JP2011012107A - Organic-inorganic composite hydrogel particle, aqueous dispersion thereof, dried particle thereof, and method for producing them - Google Patents

Organic-inorganic composite hydrogel particle, aqueous dispersion thereof, dried particle thereof, and method for producing them Download PDF

Info

Publication number
JP2011012107A
JP2011012107A JP2009155182A JP2009155182A JP2011012107A JP 2011012107 A JP2011012107 A JP 2011012107A JP 2009155182 A JP2009155182 A JP 2009155182A JP 2009155182 A JP2009155182 A JP 2009155182A JP 2011012107 A JP2011012107 A JP 2011012107A
Authority
JP
Japan
Prior art keywords
water
organic
inorganic composite
particles
hydrogel particles
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
JP2009155182A
Other languages
Japanese (ja)
Other versions
JP5398383B2 (en
Inventor
Akira Obayashi
明 王林
Kazutoshi Haraguchi
和敏 原口
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kawamura Institute of Chemical Research
Original Assignee
Kawamura Institute of Chemical Research
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kawamura Institute of Chemical Research filed Critical Kawamura Institute of Chemical Research
Priority to JP2009155182A priority Critical patent/JP5398383B2/en
Publication of JP2011012107A publication Critical patent/JP2011012107A/en
Application granted granted Critical
Publication of JP5398383B2 publication Critical patent/JP5398383B2/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Abstract

PROBLEM TO BE SOLVED: To provide new organic-inorganic composite hydrogel particles excellent in dynamic properties and mechanical characteristics and having strength and toughness, an aqueous dispersion thereof, dried particles thereof, and a method for producing them.SOLUTION: In the organic-inorganic composite hydrogel particles, water (C) is included in a three-dimensional network formed when a water-soluble organic polymer (A) obtained by polymerizing a monomer including (meth)acrylamides is combined with a water-swellable clay mineral (B). The particles are produced by undergoing a process of producing a dispersion phase including the water-swellable clay mineral (B), the monomer including (meth)acrylamides, and water (C), mixing the dispersion phase with a continuous phase including a hydrophobic dispersion medium (D) and a surfactant (E), and then performing reversed phase suspension polymerization of the monomer to produce a W/O emulsion.

Description

本発明は医薬品、化粧品、衛生用品、塗料、農業、食品、建築、土木、情報記録材料、電子部材、家庭用品などの分野で用いられる高分子ゲル粒子に関するものである。   The present invention relates to polymer gel particles used in the fields of pharmaceuticals, cosmetics, hygiene products, paints, agriculture, food, architecture, civil engineering, information recording materials, electronic members, household products and the like.

高分子ゲルは有機高分子の三次元架橋物が水や有機溶媒などの媒体を含んで膨潤したものであり、ソフトマテリアル、吸着・吸収材料、振動吸収・防振材、緩衝材、シーリング材などの材料として、工業、電子・電気、農業、土木・建築、衣料、医療・医薬、スポーツ関連などの分野で広く用いられている。近年、無機膨潤性粘土鉱物の共存下、アクリルアミド誘導体、例えば、N,N-ジメチルアクリルアミドやN-イソプロピルアクリルアミドなどを重合して得られる有機無機複合ヒドロゲルが開発され、従来にない高い力学物性を有するヒドロゲル材料として注目されている(特許文献1)。しかし、より高度な機能性を付与するため、粒子形態のミクロヒドロゲルが望まれる。   Polymer gel is a three-dimensional cross-linked organic polymer that swells with a medium such as water or organic solvent. Soft materials, adsorption / absorption materials, vibration absorption / vibration-proof materials, cushioning materials, sealing materials As a material, it is widely used in fields such as industry, electronics / electricity, agriculture, civil engineering / architecture, clothing, medicine / medicine, and sports. In recent years, organic-inorganic composite hydrogels obtained by polymerizing acrylamide derivatives such as N, N-dimethylacrylamide and N-isopropylacrylamide in the presence of inorganic swellable clay minerals have been developed and have unprecedented high mechanical properties. It attracts attention as a hydrogel material (Patent Document 1). However, in order to impart a higher degree of functionality, a microhydrogel in the form of particles is desired.

粒子形態のヒドロゲルとして、例えば、エタノールの中に、有機架橋剤の存在下、アクリルアミドとメタクリル酸との共重合で得られるサブミクロンから1ミクロンの直径をもつ単分散ヒドロゲル粒子が挙げられる(非特許文献１)。このヒドロゲル粒子には酸が含まれるため、膨潤収縮挙動においてpH応答性などの機能性を有する。また、近年、構造制御された自己組織化ナノゲルが秋吉らにより報告された(特許文献２)。すなわち、疎水性の高い分子を水溶性ポリマーに微量置換することによって水中にて自己組織的にナノメートルサイズのゲル粒子(ナノゲル)が形成される。このナノゲルは両親媒性の特性を有し、疎水性薬物の取り込みとともに、選択的なタンパク質のホストとなり得るため、ドラッグキャリアや人工シャペロンとして用いられることが期待される。しかしながら、疎水性分子の会合領域が物理架橋点となっているナノゲルの水中安定性、特に疎水基を有する分子の存在下、ナノゲルが崩壊する問題点がある。   Examples of the hydrogel in the form of particles include monodisperse hydrogel particles having a diameter of submicron to 1 micron obtained by copolymerization of acrylamide and methacrylic acid in ethanol in the presence of an organic crosslinking agent (non-patent document). Reference 1). Since this hydrogel particle contains an acid, it has functionality such as pH responsiveness in swelling and shrinkage behavior. In recent years, a self-organized nanogel having a controlled structure has been reported by Akiyoshi et al. (Patent Document 2). That is, nanometer-sized gel particles (nanogels) are formed in water in a self-organized manner by substituting a small amount of highly hydrophobic molecules with water-soluble polymers. This nanogel has amphipathic properties, and can be used as a drug carrier or artificial chaperone because it can be a selective protein host along with the uptake of a hydrophobic drug. However, there is a problem that the nanogel in which the association region of the hydrophobic molecule is a physical cross-linking point is stable in water, in particular, the nanogel collapses in the presence of a molecule having a hydrophobic group.

特開2002-053629号公報JP 2002-053629 A 特開2005-298644号公報JP 2005-298644 A

H.Kawaguchi,et al.: Polym.J.,23,955(1991)H. Kawaguchi, et al .: Polym. J., 23,955 (1991)

本発明の目的は、力学物性、機械的性質に優れ、強靱でタフネスのある新規な有機無機複合体ヒドロゲルの粒子及びその水分散体、その乾燥粒子並びにそれらの製造方法を提供することにある。   An object of the present invention is to provide a novel organic-inorganic composite hydrogel particle having excellent mechanical properties and mechanical properties, toughness and toughness, an aqueous dispersion thereof, a dry particle thereof, and a production method thereof.

本発明者らは、上記課題を解決すべく鋭意検討を重ねた。その結果、水膨潤性粘土鉱物水溶液と、水溶性有機高分子の構成成分モノマー（A')とを含む分散相と、疎水性分散媒(D)及び界面活性剤(E)を含む連続相からなる分散体を逆相懸濁重合させて得られるW/O型エマルジョンを更に媒体置換することによって有機無機複合体ヒドロゲル粒子及びその水分散体が得られること、また、上記W/O型エマルジョンの中のヒドロゲル粒子を水と相溶する有機溶媒で洗浄する又は加熱することによって水を除いた粒子粉末が得られることを見出し、本発明を完成するに至った。   The present inventors have intensively studied to solve the above problems. As a result, a dispersion phase containing a water-swellable clay mineral aqueous solution, a constituent monomer (A ′) of a water-soluble organic polymer, and a continuous phase containing a hydrophobic dispersion medium (D) and a surfactant (E) An organic-inorganic composite hydrogel particle and an aqueous dispersion thereof can be obtained by further replacing the medium with a W / O type emulsion obtained by subjecting the resulting dispersion to reverse phase suspension polymerization, and the above W / O type emulsion. The present inventors have found that particle powder from which water is removed can be obtained by washing or heating the hydrogel particles therein with an organic solvent compatible with water, and the present invention has been completed.

すなわち、本発明は、(メタ)アクリルアミド類を含むモノマーを重合した水溶性有機高分子(A)と、水膨潤性粘土鉱物(B)とが複合化して形成された三次元網目の中に水(C)が包含されている有機無機複合体ヒドロゲル粒子を提供するものである。   That is, the present invention provides water in a three-dimensional network formed by combining a water-soluble organic polymer (A) obtained by polymerizing a monomer containing (meth) acrylamides and a water-swellable clay mineral (B). An organic-inorganic composite hydrogel particle including (C) is provided.

また、本発明は、上記の有機無機複合体ヒドロゲル粒子が水中に分散した水分散体を提供するものである。   The present invention also provides an aqueous dispersion in which the organic-inorganic composite hydrogel particles are dispersed in water.

また、本発明は、水膨潤性粘土鉱物(B)と(メタ)アクリルアミド類を含むモノマーと水(C)を含む分散相を製造し、該分散相を疎水性分散媒(D)及び界面活性剤(E)を含む連続相と混合し、次いで該モノマーを逆相懸濁重合させることによりW/O型エマルジョンを製造する工程を含む上記の有機無機複合体ヒドロゲル粒子の製造方法を提供するものである。   The present invention also provides a dispersed phase containing a water-swellable clay mineral (B), a monomer containing (meth) acrylamides and water (C), and the dispersed phase is treated with a hydrophobic dispersion medium (D) and a surface active agent. A method for producing the above-mentioned organic-inorganic composite hydrogel particles comprising a step of producing a W / O emulsion by mixing with a continuous phase containing an agent (E) and then subjecting the monomer to reverse phase suspension polymerization It is.

更に、本発明は、水膨潤性粘土鉱物(B)と(メタ)アクリルアミド類を含むモノマーと水(C)を含む分散相を製造し、該分散相を疎水性分散媒(D)及び界面活性剤(E)を含む連続相と混合し、次いで該モノマーを逆相懸濁重合させることによりW/O型エマルジョンを製造し、その後、W/O型エマルジョン中の水(C)を除去する工程を含む上記の有機無機複合体粒子の製造方法を提供するものである。   Further, the present invention provides a dispersed phase containing a water-swellable clay mineral (B), a monomer containing (meth) acrylamides and water (C), and the dispersed phase is treated with a hydrophobic dispersion medium (D) and a surface active agent. Mixing with the continuous phase containing the agent (E), then producing the W / O emulsion by reverse phase suspension polymerization of the monomer, and then removing the water (C) in the W / O emulsion The manufacturing method of said organic-inorganic composite particle | grains containing is provided.

本発明によれば力学物性、機械的性質に優れ、強靱でタフネスのある新規な有機無機複合体ヒドロゲルの粒子及びその水分散体、その乾燥粒子を得ることができる。このような粒子は下記のような種々の用途において利用可能である。   According to the present invention, particles of a novel organic-inorganic composite hydrogel having excellent mechanical properties and mechanical properties, toughness and toughness, an aqueous dispersion thereof, and dried particles thereof can be obtained. Such particles can be used in various applications as described below.

たとえば、本発明で得られるN-イソプロピルアクリルアミド系の有機無機複合体ヒドロゲル粒子は、下限臨界共溶温度(LCST)を有するため、水中で温度変化によって体積や透明性が大きく変化する。この性質を利用して、ドラッグデリバリーシステム(DDS)をはじめとするバイオ領域での有用性が期待される。また、カルボン酸塩構造又はスルホン酸塩構造を有する有機無機複合体ヒドロゲル粒子は極めて高い水膨潤性を有するため、新規な高吸水性粒子として、衛生用品(紙おむつ、生理ナプキンなど)を始め、吸水材料、保水剤、脱水剤、結露防止剤などの用途に広く用いることができる。また、ジメチルアクリルアミド系の有機無機複合体粉末は、ポリエチレングリコール水溶液中に優れた水膨潤性と力学物性を有するヒドロゲルフィルムを形成するため、創傷被覆材としての用途展開が可能になった。   For example, the N-isopropylacrylamide-based organic-inorganic composite hydrogel particles obtained in the present invention have a lower critical solution temperature (LCST), so that the volume and transparency greatly change depending on temperature changes in water. Utilizing this property, it is expected to be useful in the bio field including drug delivery systems (DDS). In addition, the organic-inorganic composite hydrogel particles having a carboxylate structure or a sulfonate structure have extremely high water swellability, so as new superabsorbent particles, hygiene products (paper diapers, sanitary napkins, etc.), water absorption It can be widely used for applications such as materials, water retention agents, dehydrating agents, and anti-condensation agents. In addition, the dimethylacrylamide organic-inorganic composite powder forms a hydrogel film having excellent water swellability and mechanical properties in an aqueous polyethylene glycol solution, so that it can be used as a wound dressing.

特に、本発明の製造方法によれば、球形の有機無機複合体ヒドロゲル粒子及びその乾燥体を得ることができる。球形の形状を有する粒子は、流動性に優れ、高密度充填を行うことができる。したがって、上記の用途において使用する場合、成形性に優れ、コンパクトで均質な製品を製造することが可能であり産業上優れた効果を発揮できる。   In particular, according to the production method of the present invention, spherical organic-inorganic composite hydrogel particles and dried products thereof can be obtained. Particles having a spherical shape are excellent in fluidity and can be filled with high density. Therefore, when used in the above applications, it is possible to produce a compact and homogeneous product having excellent moldability and exhibiting excellent industrial effects.

実施例1で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 1, taken with a polarizing microscope. 実施例2で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 2 taken with a polarizing microscope. 実施例4で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 4 taken with a polarizing microscope. 実施例5で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 5 taken with a polarizing microscope. 実施例6で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。6 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 6 taken with a polarizing microscope. 実施例7で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。6 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 7 taken with a polarizing microscope. 実施例8で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。6 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 8 taken with a polarizing microscope. 実施例12で得られる有機無機複合体ヒドロゲル粒子の食塩水分散体を偏光顕微鏡にて撮影した写真である。4 is a photograph of a saline dispersion of organic-inorganic composite hydrogel particles obtained in Example 12, taken with a polarizing microscope. 実施例14で得られる有機無機複合体ヒドロゲル粒子の食塩水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of a saline dispersion of organic-inorganic composite hydrogel particles obtained in Example 14 taken with a polarizing microscope. 実施例17で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 17, taken with a polarizing microscope. 実施例18で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 18, taken with a polarizing microscope. 実施例19で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 19, taken with a polarizing microscope. 実施例21で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 21, taken with a polarizing microscope. 実施例23で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 23 taken with a polarizing microscope. 実施例24で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 24 taken with a polarizing microscope. 実施例25で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 25 taken with a polarizing microscope. 実施例26で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 26 taken with a polarizing microscope. 実施例27で得られる有機無機複合体ヒドロゲル粒子の食塩水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of a saline dispersion of organic-inorganic composite hydrogel particles obtained in Example 27 taken with a polarizing microscope. 実施例27で得られる有機無機複合体ヒドロゲル粒子の水分散体を偏光顕微鏡にて撮影した写真である。2 is a photograph of an aqueous dispersion of organic-inorganic composite hydrogel particles obtained in Example 27 taken with a polarizing microscope. 実施例7で得られる有機無機複合体ヒドロゲル粒子水分散体の光透過率の温度依存性を示す図である。FIG. 6 is a graph showing the temperature dependence of the light transmittance of the organic-inorganic composite hydrogel particle aqueous dispersion obtained in Example 7. 実施例14で得られる有機無機複合体ヒドロゲル粒子のFT-IRスペクトルである。2 is an FT-IR spectrum of organic-inorganic composite hydrogel particles obtained in Example 14. 実施例16で得られる有機無機複合体ヒドロゲル粒子のFT-IRスペクトルである。4 is an FT-IR spectrum of organic-inorganic composite hydrogel particles obtained in Example 16. 実施例22で得られる加水分解ヒドロゲル粒子のFT-IRスペクトルである。2 is an FT-IR spectrum of hydrolyzed hydrogel particles obtained in Example 22. 実施例23で得られる有機無機複合体ヒドロゲル粒子のFT-IRスペクトルである。2 is an FT-IR spectrum of organic-inorganic composite hydrogel particles obtained in Example 23. FIG. 実施例28で得られる有機無機複合体粉末のSEM写真である。3 is a SEM photograph of the organic-inorganic composite powder obtained in Example 28. 比較例1で得られる有機無機複合体粉末のSEM写真である。3 is a SEM photograph of the organic-inorganic composite powder obtained in Comparative Example 1. 実施例30で得られる有機無機複合体粉末のSEM写真である。3 is a SEM photograph of the organic-inorganic composite powder obtained in Example 30. 実施例32で得られる有機無機複合体粉末のSEM写真である。4 is a SEM photograph of organic-inorganic composite powder obtained in Example 32. 実施例34で得られる有機無機複合体粉末のSEM写真である。4 is a SEM photograph of the organic-inorganic composite powder obtained in Example 34. 実施例37で得られる有機無機複合体粉末のSEM写真である。4 is a SEM photograph of organic-inorganic composite powder obtained in Example 37. FIG. 実施例38で得られる有機無機複合体粉末を偏光顕微鏡にて撮影した写真である。4 is a photograph of the organic-inorganic composite powder obtained in Example 38 taken with a polarizing microscope. 実施例38で得られる有機無機複合体粉末断面のSEM写真である。4 is a SEM photograph of a cross section of an organic-inorganic composite powder obtained in Example 38.

本発明は、水膨潤性粘土鉱物水溶液と、水溶性モノマー（A’）とを含む水相を、界面活性剤(E)と疎水性分散媒(D) を含む油相中に注入して乳化させ、ラジカル重合開始剤により逆相懸濁重合して得られる油中水型(W/O型)エマルジョンから有機無機複合体ヒドロゲル粒子及びその水分散体を得るものである。   In the present invention, an aqueous phase containing a water-swellable clay mineral aqueous solution and a water-soluble monomer (A ′) is injected into an oil phase containing a surfactant (E) and a hydrophobic dispersion medium (D) to emulsify. And an organic-inorganic composite hydrogel particle and an aqueous dispersion thereof are obtained from a water-in-oil (W / O) emulsion obtained by reverse-phase suspension polymerization using a radical polymerization initiator.

本発明の有機無機複合体ヒドロゲル粒子及びその乾燥粒子の形状は特に限定されるものではないが、球状又は略球状粒子であることが好ましい。また、本明細書では、偏光顕微鏡の観察等により確認される真球状の粒子及び外見上ほぼ球形（略球形）の粒子を「球形」の粒子と表現する。   The shapes of the organic-inorganic composite hydrogel particles and the dry particles thereof are not particularly limited, but are preferably spherical or substantially spherical particles. In the present specification, true spherical particles and apparently spherical (substantially spherical) particles confirmed by observation with a polarizing microscope or the like are expressed as “spherical” particles.

本発明の有機無機複合体ヒドロゲル粒子及びその乾燥粒子である有機無機複合体粒子は、油中水型(W/O型)エマルジョンである逆相懸濁重合により製造されるものであるので、得られる粒子は微細であり、製造条件により異なるが、数μｍ程度の粒子から１ｍｍ前後の粒子まで製造可能である。   Since the organic-inorganic composite hydrogel particles of the present invention and the organic-inorganic composite particles that are dry particles thereof are produced by reverse phase suspension polymerization that is a water-in-oil (W / O) emulsion, Particles to be produced are fine and vary depending on production conditions, but can be produced from particles of about several μm to particles of around 1 mm.

本発明で用いられる有機無機複合ヒドロゲル粒子の有機高分子は、慣用の水溶性ビニル系モノマーのラジカル重合によって形成され、特に(メタ)アクリルアミド及びその誘導体、(メタ)アクリル酸及び(メタ)アクリル酸エステルから得られる重合体及び共重合体が好ましい。これらのモノマーから得られた重合体及び共重合体は、分子量が高く、また、水に分散した水膨潤性粘土鉱物（Ｂ）と水素結合やイオン結合等の非共有結合により三次元網目を形成できることから好適に用いられる。   The organic polymer of the organic-inorganic composite hydrogel particles used in the present invention is formed by radical polymerization of a conventional water-soluble vinyl monomer, and in particular, (meth) acrylamide and its derivatives, (meth) acrylic acid and (meth) acrylic acid. Polymers and copolymers obtained from esters are preferred. Polymers and copolymers obtained from these monomers have a high molecular weight, and form a three-dimensional network by water-swellable clay mineral (B) dispersed in water and non-covalent bonds such as hydrogen bonds and ionic bonds. Since it can be used, it is used suitably.

本発明の有機無機複合体ヒドロゲル粒子及びその乾燥粒子は、水に膨潤するが不溶であり、また有機溶媒にも不溶であるので水溶性有機高分子(A)と、水膨潤性粘土鉱物(B)とが複合化して三次元網目を形成しているものと推察される。   The organic-inorganic composite hydrogel particles of the present invention and the dried particles thereof swell in water but are insoluble, and also insoluble in organic solvents, so water-soluble organic polymer (A) and water-swellable clay mineral (B ) And a three-dimensional network.

(メタ)アクリルアミド及びその誘導体の具体例としては、アクリルアミド、メタクリルアミド、N-メチルアクリルアミド、N-エチルアクリルアミド、N-シクロプロピルアクリルアミド、N-イソプロピルアクリルアミド、N-メチルメタクリルアミド、N-シクロプロピルメタクリルアミド、N-イソプロピルメタクリルアミド、N,N-ジメチルアクリルアミド、N-メチル-N-エチルアクリルアミド、N-メチル-N-イソプロピルアクリルアミド、N-メチル-N-n-プロピルアクリルアミド、N,N-ジエチルアクリルアミド、アクリロイルモルフォリン、N-アクリロイルピロリディン、N-アクリロイルピペリディン、N-アクリロイルメチルホモピペラディン、N-アクリロイルメチルピペラディン、ジメチルアミノプロピルアクリルアミド、2-ヒドロキシエチルアクリルアミド、2-アクリルアミド-2-メチルプロパンスルホン酸、ダイアセトンアクリルアミドなどが例示される。その中に、有機無機複合体ヒドロゲル粒子を形成しやすいことから、N,N-ジメチルアクリルアミド及びアクリロイルモルフォリンが特に好ましい。また、水溶液中でのポリマー物性(親水性と疎水性)がLCST(下限臨界共溶温度)を持つN-イソプロピルアクリルアミド、N,N-ジエチルアクリルアミドなどは機能性の観点から好ましく用いられる。   Specific examples of (meth) acrylamide and derivatives thereof include acrylamide, methacrylamide, N-methylacrylamide, N-ethylacrylamide, N-cyclopropylacrylamide, N-isopropylacrylamide, N-methylmethacrylamide, N-cyclopropylmethacrylate. Amides, N-isopropylmethacrylamide, N, N-dimethylacrylamide, N-methyl-N-ethylacrylamide, N-methyl-N-isopropylacrylamide, N-methyl-Nn-propylacrylamide, N, N-diethylacrylamide, acryloyl Morpholine, N-acryloylpyrrolidine, N-acryloylpiperidine, N-acryloylmethylhomopiperazine, N-acryloylmethylpiperazine, dimethylaminopropylacrylamide, 2-hydroxyethylacrylamide, 2-acryl Riruamido 2-methylpropane sulfonic acid, diacetone acrylamide are exemplified. Among them, N, N-dimethylacrylamide and acryloylmorpholine are particularly preferable because they easily form organic-inorganic composite hydrogel particles. In addition, N-isopropylacrylamide, N, N-diethylacrylamide, etc., whose polymer properties (hydrophilicity and hydrophobicity) in an aqueous solution have LCST (lower critical solution temperature) are preferably used from the viewpoint of functionality.

(メタ)アクリル酸及び(メタ)アクリル酸エステルの具体例としては、アクリル酸、メタクリル酸、マレイン酸、フマル酸、イタコン酸、メチルアクリレート、エチルアクリレート、2-メトキシエチルアクリレート、2-エトキシエチルアクリレート、ヒドロキシエチルアクリレート、2-ヒドロキシプロピルアクリレート、ジメチルアミノエチルアクリレート、ジメチルアミノエチルメタクリレート、ジエチルアミノエチルメタクリレートなどが挙げられる。これらのモノマーは単独でヒドロゲル粒子を形成しないが、共重合モノマーとしてヒドロゲル粒子に優れる水膨潤性などの機能性を与えるため、好ましく用いられる。   Specific examples of (meth) acrylic acid and (meth) acrylic acid ester include acrylic acid, methacrylic acid, maleic acid, fumaric acid, itaconic acid, methyl acrylate, ethyl acrylate, 2-methoxyethyl acrylate, 2-ethoxyethyl acrylate Hydroxyethyl acrylate, 2-hydroxypropyl acrylate, dimethylaminoethyl acrylate, dimethylaminoethyl methacrylate, diethylaminoethyl methacrylate, and the like. Although these monomers do not form hydrogel particles by themselves, they are preferably used because they give functionalities such as water swellability superior to hydrogel particles as copolymerization monomers.

有機無機複合体ヒドロゲル粒子にアミノ基を持たせるため、アミノ基を有するモノマーとアクリルアミド誘導体との共重合が有効である。アミノ基を有するモノマーとしては、上述のジメチルアミノプロピルアクリルアミド、ジメチルアミノエチルアクリレート、ジメチルアミノエチルメタクリレート、ジエチルアミノエチルメタクリレートが用いられる。また、アミノ基を有するモノマーとアクリルアミド誘導体との共重合組成において、アミノ基を有するモノマーの共重合比率が高すぎると、ヒドロゲル粒子は得られない場合がある。一方、その共重合比率が低すぎると、本発明のヒドロゲル粒子の機能性は発揮出来なくなる。従って、有機高分子(A)中のアミノ基を有するモノマーの共重合比率としては、モノマー全体に対して0.1〜50モル%であることが好ましく、より好ましくは0.3〜40モル%であり、特に好ましくは0.5〜30モル%であり、1〜20モル%であることが最も好ましい。   Copolymerization of a monomer having an amino group and an acrylamide derivative is effective in order to give the organic / inorganic composite hydrogel particles an amino group. As the monomer having an amino group, the above-mentioned dimethylaminopropylacrylamide, dimethylaminoethyl acrylate, dimethylaminoethyl methacrylate, and diethylaminoethyl methacrylate are used. Moreover, in the copolymerization composition of the monomer which has an amino group, and an acrylamide derivative, when the copolymerization ratio of the monomer which has an amino group is too high, a hydrogel particle may not be obtained. On the other hand, if the copolymerization ratio is too low, the functionality of the hydrogel particles of the present invention cannot be exhibited. Therefore, the copolymerization ratio of the monomer having an amino group in the organic polymer (A) is preferably 0.1 to 50 mol%, more preferably 0.3 to 40 mol%, particularly with respect to the whole monomer. Preferably it is 0.5-30 mol%, and it is most preferable that it is 1-20 mol%.

また、カルボン酸基又はスルホン酸基を有するモノマーとアクリルアミド誘導体との共重合によって有機無機複合体ヒドロゲル粒子にカルボン酸塩構造又はスルホン酸塩構造を導入できる。カルボン酸基又はスルホン酸基を有するモノマーとしては、アクリル酸や2-アクリルアミド-2-メチルプロパンスルホン酸などが挙げられる。これらのカルボン酸基又はスルホン酸基を有するモノマーはそのまま使うと、粘土鉱物の凝集が起こりやすいため、予め炭酸ナトリウムなどで中和してから共重合に供することが好ましい。また、これらのカルボン酸基又はスルホン酸基を有するモノマーとアクリルアミド誘導体との共重合組成において、カルボン酸基又はスルホン酸基を有するモノマーの共重合比率が高すぎると、ヒドロゲル粒子は得られない場合がある。一方、その共重合比率が低すぎると、本発明のヒドロゲル粒子の機能性は発揮出来なくなる。従って、有機高分子(A)中のカルボン酸基又はスルホン酸基を有する重合性モノマーの共重合比率としては、モノマー全体に対して0.1〜70モル%であることが好ましく、より好ましくは0.3〜50モル%であり、特に好ましくは0.5〜30モル%である。   Moreover, a carboxylate structure or a sulfonate structure can be introduced into the organic-inorganic composite hydrogel particles by copolymerization of a monomer having a carboxylic acid group or a sulfonic acid group and an acrylamide derivative. Examples of the monomer having a carboxylic acid group or a sulfonic acid group include acrylic acid and 2-acrylamido-2-methylpropanesulfonic acid. If these monomers having a carboxylic acid group or a sulfonic acid group are used as they are, aggregation of clay minerals is likely to occur. Therefore, it is preferable to neutralize with sodium carbonate or the like before use for copolymerization. Moreover, in the copolymerization composition of the monomer having carboxylic acid group or sulfonic acid group and the acrylamide derivative, if the copolymerization ratio of the monomer having carboxylic acid group or sulfonic acid group is too high, hydrogel particles cannot be obtained. There is. On the other hand, if the copolymerization ratio is too low, the functionality of the hydrogel particles of the present invention cannot be exhibited. Therefore, the copolymerization ratio of the polymerizable monomer having a carboxylic acid group or a sulfonic acid group in the organic polymer (A) is preferably 0.1 to 70 mol% with respect to the whole monomer, more preferably 0.3 to 50 mol%, particularly preferably 0.5 to 30 mol%.

更に、高密度のカルボン酸塩構造を有機無機複合体ヒドロゲル球状粒子に導入する場合、加水分解性モノマーとアクリルアミド誘導体とを共重合して加水分解性基を有するヒドロゲル粒子を合成する方法がある。加水分解性モノマーとしては、アクリルアミドや2-メトキシエチルアクリレートなどが好適に用いられる。得られたヒドロゲル粒子を苛性アルカリで加水分解させて、粒子中のアミド基又はエステル基の少なくとも一部をカルボン酸塩構造に変換することによってカルボン酸塩構造を有する有機無機複合体ヒドロゲル粒子を得ることができる。加水分解に用いられるヒドロゲル粒子のモノマー組成、即ち、加水分解性モノマーとアクリルアミド誘導体との共重合比率は、用いる加水分解性モノマーの種類によって適宜設定する。アクリルアミドを使用する場合、モノマー全体に対して0.1〜100モル%で広範囲に設定することができる。アクリルアミドの含有率が高くなるにつれ、加水分解することによってカルボン酸塩構造の基の密度が上がり、ヒドロゲルの水膨潤性は著しく増加する。一方、(メタ)アクリル酸エステル、例えば2-メトキシエチルアクリレートを用いた場合、その共重合比率としては、モノマー全体に対して0.1〜70モル%であることが好ましく、より好ましくは0.5〜60モル%であり、特に好ましくは10〜50モル%である。0.1モル%未満では、加水分解後のヒドロゲルの水膨潤性は不十分であり、70モル%を超えると、ヒドロゲル粒子が形成されない場合がある。   Furthermore, when introducing a high-density carboxylate structure into the organic-inorganic composite hydrogel spherical particles, there is a method of synthesizing hydrogel particles having a hydrolyzable group by copolymerizing a hydrolyzable monomer and an acrylamide derivative. As the hydrolyzable monomer, acrylamide, 2-methoxyethyl acrylate and the like are preferably used. The obtained hydrogel particles are hydrolyzed with caustic, and at least a part of the amide group or ester group in the particles is converted into a carboxylate structure to obtain an organic-inorganic composite hydrogel particle having a carboxylate structure. be able to. The monomer composition of the hydrogel particles used for the hydrolysis, that is, the copolymerization ratio of the hydrolyzable monomer and the acrylamide derivative is appropriately set depending on the type of the hydrolyzable monomer used. When acrylamide is used, it can be set in a wide range from 0.1 to 100 mol% with respect to the whole monomer. As the acrylamide content increases, hydrolysis increases the density of the carboxylate structure groups and the water swellability of the hydrogel increases significantly. On the other hand, when (meth) acrylic acid ester such as 2-methoxyethyl acrylate is used, the copolymerization ratio is preferably 0.1 to 70 mol%, more preferably 0.5 to 60 mol, based on the whole monomer. %, Particularly preferably 10 to 50 mol%. If it is less than 0.1 mol%, the hydroswellability of the hydrogel after hydrolysis is insufficient, and if it exceeds 70 mol%, hydrogel particles may not be formed.

また、生体適合性に優れるポリエチレングリコール(PEG)を本発明の有機無機複合体ヒドロゲル球状粒子に導入する場合、式（１）で表されるアクリルモノマーが共重合モノマーとして使用される。式(1)のモノマーはイオン性を持たないため耐塩性にも優れ、得られるヒドロゲル粒子の高い食塩水膨潤性が期待される。   Further, when polyethylene glycol (PEG) having excellent biocompatibility is introduced into the organic-inorganic composite hydrogel spherical particles of the present invention, an acrylic monomer represented by the formula (1) is used as a copolymerization monomer. Since the monomer of formula (1) does not have ionicity, it has excellent salt resistance, and the resulting hydrogel particles are expected to have high salt swellability.

Figure 2011012107
（式中、Ｒ１は、水素原子又はメチル基、Ｒ２は炭素数２又は３のアルキレン基、ｎは３〜９９の整数、Ｙはメトキシ基又は水酸基を表す。）
Figure 2011012107
 (Wherein R 1 represents a hydrogen atom or a methyl group, R 2 represents an alkylene group having 2 or 3 carbon atoms, n represents an integer of 3 to 99, and Y represents a methoxy group or a hydroxyl group.)

優れる生体適合性及び膨潤性を得るため、上記の式（１）で表されるアクリルモノマーは全モノマーに対して、その使用比率が好ましくは１質量％〜７０質量％であり、より好ましくは３質量％〜６０質量％であり、５質量％〜５０質量％が特に好ましい。また、式（１）で表されるアクリルモノマーのエチレングリコール繰り返し単位数は３〜９９個のものを適宜に選択することができる。一般的には、エチレングリコール繰り返し単位数を増えることにつれ、得られる有機無機複合ヒドロゲル粒子の食塩水での膨潤度が高くなると考えられる。また、PEG側鎖を有する有機無機複合体ヒドロゲル粒子の水膨潤性を更に向上させるため、カルボン酸基又はスルホン酸基を導入することが有効である。例えば、上記の式（１）で表されるアクリルモノマーとアクリルアミド誘導体にアクリル酸ナトリウムを更に加え、共重合させると、PEG側鎖とカルボン酸塩構造を有する有機無機複合体ヒドロゲル粒子が得られる。   In order to obtain excellent biocompatibility and swellability, the use ratio of the acrylic monomer represented by the above formula (1) is preferably 1% by mass to 70% by mass, more preferably 3%, based on all monomers. % By mass to 60% by mass, particularly preferably 5% by mass to 50% by mass. The number of ethylene glycol repeating units of the acrylic monomer represented by formula (1) can be appropriately selected from 3 to 99. In general, as the number of ethylene glycol repeating units is increased, the degree of swelling of the resulting organic-inorganic composite hydrogel particles in saline is considered to increase. In order to further improve the water swellability of the organic-inorganic composite hydrogel particles having a PEG side chain, it is effective to introduce a carboxylic acid group or a sulfonic acid group. For example, when an acrylic monomer represented by the above formula (1) and an acrylamide derivative are further added with sodium acrylate and copolymerized, organic-inorganic composite hydrogel particles having a PEG side chain and a carboxylate structure are obtained.

本発明に用いる水膨潤性粘土鉱物（Ｂ）は、水に膨潤し均一分散可能なものであり、特に好ましくは水中で分子状(単一層)またはそれに近いレベルで均一分散可能な層状粘土鉱物である。例えば、水膨潤性スメクタイトや水膨潤性雲母などが用いられ、具体的には、ナトリウムを層間イオンとして含む水膨潤性ヘクトライト、水膨潤性モンモリロナイト、水膨潤性サポナイト、水膨潤性合成雲母などが挙げられる。これらの粘土鉱物は、水溶性有機高分子のモノマーが重合する前の水溶液中で微細、且つ均一に分散していることが必要であり、特に水溶液中に単位層レベルで分散していることが望ましい。ここで、水溶液中に粘土鉱物の沈殿となるような粘土鉱物凝集体がないことが必要であり、より好ましくは1〜10層程度のナノオーターの厚みで分散しているもの、特に好ましくは1又は2層程度の厚みで分散しているものである。また、反応系(水相)が増粘しやすいまたは粘土鉱物の添加量が多い場合、油相中での乳化分散が困難になるため、ピロリン酸ナトリウムを予め配合された低粘度の粘土鉱物は好ましく用いられる。   The water-swellable clay mineral (B) used in the present invention is a layered clay mineral that can swell and uniformly disperse in water, and is particularly preferably a layered clay mineral that can be uniformly dispersed in water at a molecular level (single layer) or a level close thereto. is there. For example, water-swellable smectite or water-swellable mica is used. Specifically, water-swellable hectorite containing sodium as an interlayer ion, water-swellable montmorillonite, water-swellable saponite, water-swellable synthetic mica, etc. Can be mentioned. These clay minerals need to be finely and uniformly dispersed in an aqueous solution before the monomer of the water-soluble organic polymer is polymerized. In particular, the clay mineral must be dispersed at the unit layer level in the aqueous solution. desirable. Here, it is necessary that there is no clay mineral aggregate that causes precipitation of clay mineral in the aqueous solution, more preferably one having a thickness of about 1 to 10 layers dispersed, particularly preferably 1 or It is dispersed with a thickness of about two layers. In addition, when the reaction system (aqueous phase) tends to thicken or a large amount of clay mineral is added, it becomes difficult to emulsify and disperse in the oil phase. Preferably used.

本発明の有機無機複合体ヒドロゲル粒子における水溶性有機高分子（Ａ）と水に均一分散可能な水膨潤性粘土鉱物（Ｂ）との比率は、（Ａ）と（Ｂ）とからなる三次元網目を有する有機無機複合体ヒドロゲル粒子が調製されれば良く、また用いる（Ａ）や（Ｂ）の種類によっても異なり必ずしも限定されないが、ヒドロゲル粒子合成の容易さや均一性の点からは、好ましくは前記水膨潤性粘土鉱物（Ｂ）と前記水溶性有機高分子（Ａ）の質量比（（Ｂ）／（Ａ））は0.01〜10である。また、より好ましくは（Ｂ）／（Ａ）の質量比が0.01〜5、特に好ましくは0.03〜3である。   The ratio of the water-soluble organic polymer (A) to the water-swellable clay mineral (B) that can be uniformly dispersed in water in the organic-inorganic composite hydrogel particles of the present invention is a three-dimensional structure comprising (A) and (B). The organic-inorganic composite hydrogel particles having a network may be prepared, and are not necessarily limited depending on the types of (A) and (B) used. From the viewpoint of the ease of synthesis and uniformity of the hydrogel particles, The mass ratio ((B) / (A)) of the water-swellable clay mineral (B) and the water-soluble organic polymer (A) is 0.01 to 10. More preferably, the mass ratio of (B) / (A) is 0.01 to 5, particularly preferably 0.03 to 3.

（Ｂ）／（Ａ）の質量比が0.01未満では、本発明のヒドロゲル粒子が柔らかすぎてお互い合体する場合が多く、10を越えては、水相の粘度が高くて乳化しにくいなどの製造上の問題が生じる場合がある。一方、(A)+(B)に対する(C)水の比率は、重合過程での水量調整、もしくはその後の膨潤や乾燥により、目的に応じて広い範囲で任意に設定できる。   When the mass ratio of (B) / (A) is less than 0.01, the hydrogel particles of the present invention are often too soft and coalesce with each other. When the mass ratio exceeds 10, the aqueous phase has a high viscosity and is difficult to emulsify. The above problem may occur. On the other hand, the ratio of (C) water to (A) + (B) can be arbitrarily set within a wide range according to the purpose by adjusting the amount of water in the polymerization process or by subsequent swelling or drying.

本発明において水相中の水溶性モノマーのラジカル重合反応は、ラジカル重合開始剤及び／又は放射線照射など公知の方法により行わせることができる。ラジカル重合開始剤及び触媒としては、公知慣用のラジカル重合開始剤及び触媒を適時選択して用いることができる。好ましくは水分散性を有し、系全体に均一に含まれるものが用いられる。特に好ましくは層状に剥離した水膨潤性粘土鉱物(B)と強い相互作用を有するラジカル重合開始剤である。   In the present invention, the radical polymerization reaction of the water-soluble monomer in the aqueous phase can be performed by a known method such as a radical polymerization initiator and / or radiation irradiation. As the radical polymerization initiator and the catalyst, known and commonly used radical polymerization initiators and catalysts can be appropriately selected and used. Preferably, those having water dispersibility and uniformly contained in the entire system are used. Particularly preferred is a radical polymerization initiator having a strong interaction with the water-swellable clay mineral (B) exfoliated in layers.

具体的には、重合開始剤として、水溶性の過酸化物、例えばペルオキソ二硫酸カリウムやペルオキソ二硫酸アンモニウム、水溶性のアゾ化合物、例えば、VA-044, V-50, V-501の他、ポリエチレンオキシド鎖を有する水溶性のラジカル開始剤などが挙げられる。一方、触媒としては、3級アミン化合物であるN,N,N’,N’-テトラメチルエチレンジアミンやβ-ジメチルアミノプロピオ二トリルなどが用いられる。   Specifically, as the polymerization initiator, water-soluble peroxides such as potassium peroxodisulfate and ammonium peroxodisulfate, water-soluble azo compounds such as VA-044, V-50, V-501, And water-soluble radical initiators having an ethylene oxide chain. On the other hand, a tertiary amine compound such as N, N, N ′, N′-tetramethylethylenediamine or β-dimethylaminopropionitryl is used as the catalyst.

重合温度は、開始剤の種類にあわせて0℃〜100℃の範囲で設定できる。重合時間も他の重合条件によって異なり、一般に数十秒〜数十時間の間で行われる。   The polymerization temperature can be set in the range of 0 ° C. to 100 ° C. according to the type of initiator. The polymerization time varies depending on other polymerization conditions, and is generally carried out for several tens of seconds to several tens of hours.

本発明において疎水性分散媒(D)は、水に相溶しない、重合反応に不活性であれば、いかなるものも使用することができる。例えば、脂肪族、脂環族、芳香族の炭化水素又はシリコンオイルを単独又は併用して用いられる。具体例としては、n-ペンタン、n-ヘキサン、n-へブタン、n-オクタン、シクロペンタン、シクロヘキサン、メチルシクロヘキサン、トルエン、ベンゼン、キシレン、流動パラフィン、鉱油などが挙げられる。その中、流動パラフィンが特に好ましく用いられる。   In the present invention, any hydrophobic dispersion medium (D) may be used as long as it is incompatible with water and inert to the polymerization reaction. For example, aliphatic, alicyclic, aromatic hydrocarbons or silicone oils are used alone or in combination. Specific examples include n-pentane, n-hexane, n-heptane, n-octane, cyclopentane, cyclohexane, methylcyclohexane, toluene, benzene, xylene, liquid paraffin, mineral oil, and the like. Among them, liquid paraffin is particularly preferably used.

本発明で用いる疎水性界面活性剤(E)としては、HLB 2〜7のソルビタン脂肪酸エステル、ソルビトール脂肪酸エステル、ショ糖脂肪酸エステル、ポリエチレングリコールの脂肪酸エステル、高級アルコールのEO付加物及びグリセリン脂肪酸エステルなどの非イオン性界面活性剤やエチルセルロースなどが挙げられ、これらの中に市販のソルビタン脂肪酸エステルであるレオドールAO-10Vが特に好ましい。添加量は、水相に対して1〜30重量%、好ましくは2〜25重量%であり、特に好ましくは4〜20重量%である。1重量%未満では、水相の乳化分散性が不十分であり、30重量%を超えると、得られるヒドロゲル粒子が細かすぎて、分離精製が困難になり好ましくない。   Examples of the hydrophobic surfactant (E) used in the present invention include HLB 2-7 sorbitan fatty acid ester, sorbitol fatty acid ester, sucrose fatty acid ester, fatty acid ester of polyethylene glycol, EO adduct of higher alcohol and glycerin fatty acid ester Nonionic surfactants, ethyl cellulose, and the like, and among them, commercially available sorbitan fatty acid ester, rheodol AO-10V, is particularly preferable. The addition amount is 1 to 30% by weight, preferably 2 to 25% by weight, particularly preferably 4 to 20% by weight, based on the aqueous phase. If it is less than 1% by weight, the emulsification and dispersibility of the aqueous phase is insufficient.

本発明の有機無機複合体ヒドロゲル粒子は、以下の方法で製造できる。有機高分子(A)のモノマーと、水に均一分散可能な水膨潤性粘土鉱物(B)と、水(C)とを含む均一溶液(水相)を調製し、重合開始剤と触媒を加えた後、速やかに界面活性剤を含む疎水性有機溶媒(油相)に注入する。乳化分散により形成された液滴の中に層状剥離した粘土鉱物(B)の共存下に(A)のモノマーの重合を行われる。重合過程で(A)のモノマーと粘土鉱物(B)との相互作用により(B)がモノマーの架橋剤の働きをして、(A)と(B)との分子レベルでの複合化が達成され、三次元網目形成によりゲル化した有機無機複合体ヒドロゲル粒子が得られる。   The organic-inorganic composite hydrogel particles of the present invention can be produced by the following method. Prepare a homogeneous solution (water phase) containing the monomer of organic polymer (A), water-swellable clay mineral (B) that can be uniformly dispersed in water, and water (C), and add a polymerization initiator and a catalyst. After that, it is immediately poured into a hydrophobic organic solvent (oil phase) containing a surfactant. The monomer (A) is polymerized in the presence of the clay mineral (B) exfoliated in layers in the droplets formed by emulsification and dispersion. (B) acts as a monomer crosslinker due to the interaction between the monomer (A) and the clay mineral (B) during the polymerization process, and (A) and (B) are combined at the molecular level. Thus, an organic-inorganic composite hydrogel particle gelled by forming a three-dimensional network is obtained.

具体的には、界面活性剤を疎水性有機溶媒に添加し溶解させた後、窒素パブリングして油相とする。一方、水中に微細分散した粘土鉱物(B)の水溶液に、アクリルアミド誘導体を加え、窒素バブリングする。次に反応系を低温にして重合触媒(TEMED)とラジカル重合開始剤(KPS水溶液)を添加混合させた後、速やかに上記の油相に加え、攪拌下乳化分散と共に所定温度と時間で重合を行わせることによって、W/O型エマルジョンが得られる。   Specifically, a surfactant is added to a hydrophobic organic solvent and dissolved, and then nitrogen publishing is performed to form an oil phase. On the other hand, an acrylamide derivative is added to an aqueous solution of clay mineral (B) finely dispersed in water, and nitrogen bubbling is performed. Next, the reaction system is cooled to a low temperature and the polymerization catalyst (TEMED) and radical polymerization initiator (KPS aqueous solution) are added and mixed, and then quickly added to the above oil phase and polymerized at a predetermined temperature and time with emulsification and dispersion under stirring. By carrying out, a W / O type emulsion is obtained.

アミノ基を有する有機無機複合体ヒドロゲル粒子において、水相調製時でのアミノ基を有するモノマーの添加順序が重要である。先にアクリルアミド誘導体と一緒にアミノ基含有(メタ)アクリレートを添加すると、粘土鉱物が(メタ)アクリレートのアミノ基と強い相互作用により凝集を生じてしまう。粘土鉱物の凝集を最小限に抑えるため、(メタ)アクリルアミド誘導体を先に粘土鉱物水分散液に加え、続いてアミノ基含有(メタ)アクリレートと重合開始剤を一度に添加させること又は重合開始剤を加えた直後にアミノ基含有(メタ)アクリレートを添加させることによって、モノマーの分散と共にラジカル重合が始まり、短時間で油相中の水滴をゲル化させる方法が有効に用いられる。   In the organic-inorganic composite hydrogel particles having an amino group, the order of addition of the monomer having an amino group at the time of preparing the aqueous phase is important. When the amino group-containing (meth) acrylate is added together with the acrylamide derivative, the clay mineral is agglomerated due to a strong interaction with the amino group of (meth) acrylate. In order to minimize the aggregation of clay minerals, the (meth) acrylamide derivative is first added to the clay mineral aqueous dispersion, and then the amino group-containing (meth) acrylate and the polymerization initiator are added at once, or the polymerization initiator. By adding the amino group-containing (meth) acrylate immediately after the addition of the radical, radical polymerization starts with the dispersion of the monomer, and a method of gelling water droplets in the oil phase in a short time is effectively used.

また、カルボン酸塩構造又はスルホン酸塩構造を有する有機無機複合体ヒドロゲル粒子においても、カルボン酸塩基又はスルホン酸塩基を有するモノマーの添加順序は重要である。先にアクリルアミド誘導体と一緒にカルボン酸塩基又はスルホン酸塩基を有する重合性モノマーを添加すると、粘土鉱物とカルボン酸塩基との相互作用により、反応系が著しく増粘し、ゲル化する場合もある。そのため、水相は油相に乳化分散できなくなり、ヒドロゲル粒子が得られない。反応系の増粘を抑えるため、(メタ)アクリルアミド誘導体を先に粘土鉱物水分散液に加え、窒素パブリングしてから、カルボン酸塩基又はスルホン酸塩基を有するモノマーと重合開始剤を一度に添加させること又は重合開始剤を加えた直後にカルボン酸塩基又はスルホン酸塩基を有するモノマーを添加させることによって、水相が増粘していない内に油相に乳化分散させることができる。   Also in the organic-inorganic composite hydrogel particles having a carboxylate structure or a sulfonate structure, the order of addition of the monomer having a carboxylate group or a sulfonate group is important. When a polymerizable monomer having a carboxylic acid group or a sulfonic acid group is added together with the acrylamide derivative first, the reaction system may be significantly thickened and gelled due to the interaction between the clay mineral and the carboxylic acid group. Therefore, the water phase cannot be emulsified and dispersed in the oil phase, and hydrogel particles cannot be obtained. In order to suppress the thickening of the reaction system, the (meth) acrylamide derivative is first added to the clay mineral aqueous dispersion, and after nitrogen publishing, a monomer having a carboxylate group or a sulfonate group and a polymerization initiator are added at once. Alternatively, by adding a monomer having a carboxylate group or a sulfonate group immediately after adding the polymerization initiator, the aqueous phase can be emulsified and dispersed in the oil phase while the viscosity is not increased.

上述の方法で得られたW/O型エマルジョンに水を加え、遠心分離することによってヒドロゲル粒子を下層の水層に沈降させ、疎水性界面活性剤を含む上層の油層をデカンテーションにより除去する。更に等量の水とヘキサンを加え、ヒドロゲル粒子を攪拌洗浄し、遠心分離することによって残存の界面活性剤を含む上澄み溶液を除く。この操作を二三回繰り返してから水を加え、攪拌によりヒドロゲル粒子を水に分散させ、界面活性剤を殆ど含まないヒドロゲル粒子の水分散体が得られる。偏光顕微鏡の観察によって、得られたヒドロゲル粒子がミクロオーダーの球状又は略球状粒子であり、お互いに殆ど融着合体せず、独立して水の中に分散していることがわかった。また、アミノ基やカルボン酸塩構造やスルホン酸塩構造などを有するヒドロゲル粒子は水の中に著しく膨潤する場合があるため、水分散体を調製するには水の代わりに食塩水を用いることが好ましい。食塩水の中にイオン性基を有するヒドロゲル粒子の膨潤が抑えられ、粒子径及び粒子形状は保つことができる。   Water is added to the W / O type emulsion obtained by the above-mentioned method, and the hydrogel particles are precipitated in the lower aqueous layer by centrifuging, and the upper oil layer containing the hydrophobic surfactant is removed by decantation. Further, an equal amount of water and hexane are added, the hydrogel particles are stirred and washed, and the supernatant solution containing the remaining surfactant is removed by centrifugation. After repeating this operation a few times, water is added and the hydrogel particles are dispersed in water by stirring to obtain an aqueous dispersion of hydrogel particles containing almost no surfactant. By observation with a polarizing microscope, it was found that the obtained hydrogel particles were micro-order spherical or nearly spherical particles, hardly fused together with each other, and independently dispersed in water. In addition, since hydrogel particles having amino groups, carboxylate structures, sulfonate structures, etc. may swell significantly in water, it is necessary to use saline instead of water to prepare an aqueous dispersion. preferable. Swelling of hydrogel particles having an ionic group in the saline is suppressed, and the particle diameter and particle shape can be maintained.

一方、加水分解性基を有する有機無機複合ヒドロゲル粒子の加水分解において、まず、上述の逆相懸濁重合によりW/O型エマルジョンを合成し、そして遠心分離の分離精製工程を経て、ヒドロゲル粒子の水分散体を調製する。得られた粒子の水分散体にアルカリを添加し、溶解した後、所定温度と時間で加水分解反応を行う。アルカリ加水分解においては通常の強塩基が用いられる。例えば、水酸化ナトリウム、水酸化カリウム、水酸化リチウム、水酸化カルシウム、アンモニアなどが挙げられる。実用性や水溶性の観点から、水酸化ナトリウムが特に好ましい。アルカリの使用量は、加水分解性モノマーの含有比率に応じて適宜使用されるが、通常、理論量より過剰量で使用される。加水分解温度は30℃〜100℃、好ましくは50℃〜90℃であり、温度が低すぎると加水分解反応が良好に進行せず、逆に温度が高すぎるとヒドロゲル粒子の形状が保持できない場合があり、好ましくない。また、感温性モノマー、例えばN-イソプロピルアクリルアミドやN,N-ジエチルアクリルアミドなどを用いて得られたヒドロゲルは、加水分解時に収縮して含水率が大きく低下したため、加水分解がなかなか進行しない問題を生じる。この場合、水と相溶する有機溶媒の添加が有効である。例えば、メタノール、エタノール、アセトン、THFなどが挙げられる。加水分解に用いるアルカリ水溶液、例えば水酸化ナトリウムの濃度は0.1N〜5Nが好ましく、特に好ましくは1Nである。加水分解反応が終わった後、過剰の水酸化ナトリウムを塩酸などで中和し、ヒドロゲルの水分散体を中性にすることができる。中和反応で生じた塩化ナトリウムは透析や遠心分離などの方法で除けられる。粒子の形状及び粒子間の融着を防ぐため、大量の水の中に透析する方法が好ましい。   On the other hand, in the hydrolysis of the organic-inorganic composite hydrogel particles having hydrolyzable groups, first, a W / O emulsion is synthesized by the above-described reversed-phase suspension polymerization, and after the separation and purification step of centrifugation, An aqueous dispersion is prepared. An alkali is added to the aqueous dispersion of particles obtained and dissolved, followed by a hydrolysis reaction at a predetermined temperature and time. A normal strong base is used in the alkaline hydrolysis. For example, sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, ammonia and the like can be mentioned. Sodium hydroxide is particularly preferable from the viewpoints of practicality and water solubility. The amount of alkali used is appropriately selected according to the content ratio of the hydrolyzable monomer, but is usually used in an excess amount from the theoretical amount. The hydrolysis temperature is 30 ° C to 100 ° C, preferably 50 ° C to 90 ° C. If the temperature is too low, the hydrolysis reaction does not proceed well. Conversely, if the temperature is too high, the shape of the hydrogel particles cannot be maintained. Is not preferable. In addition, hydrogels obtained using temperature-sensitive monomers such as N-isopropylacrylamide and N, N-diethylacrylamide have shrunk during hydrolysis and their water content has greatly decreased. Arise. In this case, it is effective to add an organic solvent that is compatible with water. For example, methanol, ethanol, acetone, THF and the like can be mentioned. The concentration of the aqueous alkali solution used for the hydrolysis, for example, sodium hydroxide is preferably 0.1N to 5N, and particularly preferably 1N. After the hydrolysis reaction is over, excess sodium hydroxide can be neutralized with hydrochloric acid or the like to make the aqueous dispersion of hydrogel neutral. Sodium chloride produced by the neutralization reaction is removed by methods such as dialysis and centrifugation. In order to prevent particle shape and fusion between particles, a method of dialysis in a large amount of water is preferable.

本発明において共重合や加水分解などの方法で得られるカルボン酸塩構造又はスルホン酸塩構造を有するヒドロゲル粒子は、酸処理することによりカルボン酸塩又はスルホン酸塩を容易にカルボン酸又はスルホン酸に変換し、カルボキシル基又はスルホン酸基を有するヒドロゲル粒子を得ることができる。例えば、カルボン酸塩構造又はスルホン酸塩構造を有するヒドロゲル粒子の水分散体に0.1〜5N塩酸を理論量より過剰量で加え、所定温度と時間で酸処理を行う。かかる酸処理温度は20℃〜80℃であり、好ましくは25℃〜50℃である。酸処理時間は酸処理温度にもよるが、一般に2〜10時間である。   In the present invention, the hydrogel particles having a carboxylate structure or a sulfonate structure obtained by a method such as copolymerization or hydrolysis can be easily converted into a carboxylic acid or a sulfonic acid by acid treatment. By converting, hydrogel particles having a carboxyl group or a sulfonic acid group can be obtained. For example, 0.1-5N hydrochloric acid is added in an excess amount from the theoretical amount to an aqueous dispersion of hydrogel particles having a carboxylate structure or a sulfonate structure, and acid treatment is performed at a predetermined temperature and time. The acid treatment temperature is 20 ° C to 80 ° C, preferably 25 ° C to 50 ° C. Although the acid treatment time depends on the acid treatment temperature, it is generally 2 to 10 hours.

一方、本発明は、上述の各種ヒドロゲル粒子に対して、水と相溶する有機溶剤を用いて洗浄することによってヒドロゲル粒子中の水分を除き、有機無機複合体粒子粉末を得ることができる。水と相溶する有機溶剤としては、アセトン、メタノール、エタノール、イソプロパノール、テトラヒドロフラン(THF)、N,N-ジメチルホルムアミド(DMF)、ジメチルスルホキシド(DMSO)などが挙げられる。具体的な洗浄方法としては、まず上述のW/O型エマルジョンを遠心分離でその中の粒子を沈降させて、デカンテーションにより上澄みを除去する。次に回収した粒子をアセトンで二三回洗浄して、濾過により水分を含まない粒子粉末を回収し、熱風乾燥させた。また、アセトンの中に膨潤するようなNIPAMやACMO系のゲル粒子では、アセトン洗浄した後、貧溶媒ヘキサンで更に洗浄することによってサラサラな粉末が得られる。   On the other hand, the present invention can remove the water in the hydrogel particles by washing the above-mentioned various hydrogel particles with an organic solvent that is compatible with water to obtain organic-inorganic composite particle powder. Examples of the organic solvent compatible with water include acetone, methanol, ethanol, isopropanol, tetrahydrofuran (THF), N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and the like. As a specific washing method, first, the above-mentioned W / O emulsion is centrifuged to precipitate particles therein, and the supernatant is removed by decantation. Next, the collected particles were washed with acetone a few times, and the powder particles containing no moisture were collected by filtration and dried with hot air. For NIPAM or ACMO gel particles that swell in acetone, a clean powder can be obtained by further washing with a poor solvent hexane after washing with acetone.

また、水の沸点以上の疎水性有機溶媒、例えば、流動パラフィンを用いたW/O型エマルジョンにおいで、エマルジョンを攪拌しながら加熱することによって、流動パラフィン中のヒドロゲル粒子の含水率を調製することができる。水を全部除くと、ヒドロゲルの乾燥粒子になる。濾過又は遠心分離をして、更にヘキサン洗浄することにより流動パラフィンを除き、乾燥してヒドロゲル乾燥粒子の粉末が得られる。   In addition, the water content of hydrogel particles in liquid paraffin should be adjusted by heating the emulsion while stirring in a hydrophobic organic solvent with a boiling point of water or higher, such as a W / O emulsion using liquid paraffin. Can do. When all the water is removed, it becomes dry particles of the hydrogel. Liquid paraffin is removed by filtering or centrifuging, and further washed with hexane, and dried to obtain hydrogel dry particle powder.

上述の方法で得られた各種の有機無機複合体粉末をSEMで観察したところ、殆ど球状又は略球状の粒子であり、その中、一部中空状の粒子もあった。従来の機械粉砕により得られた無定形粒子と比べて、本発明の球状粒子はより付加価値の高いものと考えられる。   When various organic-inorganic composite powders obtained by the above-mentioned method were observed with an SEM, they were almost spherical or almost spherical particles, and some of them were hollow. Compared with amorphous particles obtained by conventional mechanical pulverization, the spherical particles of the present invention are considered to have higher added value.

本発明の有機無機複合体ヒドロゲル粒子には、低温側で透明及び／又は体積膨潤状態にあり、且つ高温側で不透明及び／又は体積収縮状態となる臨界温度(Tc)を有し、Tcを境にした上下の温度変化により透明性や体積を可逆的に変化できる特徴を有するものが含まれる。このような有機無機複合体ヒドロゲル粒子は有機モノマーとして水溶液中でLCST(下限臨界共溶温度)を示す感温性モノマー、例えばN-イソプロピルアクリルアミドを用いて調製できる。得られるヒドロゲル粒子の水分散体は34℃付近のLCST温度を持ち、それより高い温度、例えば50℃では水分散体が白濁になり、その球状粒子の直径が25℃の時に比べて1/3まで小さくなった。このヒドロゲル粒子の温度応答性を利用して、ドラッグデリバリーシステム(DDS)への応用展開が期待される。   The organic-inorganic composite hydrogel particles of the present invention have a critical temperature (Tc) that is transparent and / or volume swelled on the low temperature side and opaque and / or volume contracted on the high temperature side. Those having the characteristic that the transparency and volume can be reversibly changed by changing the temperature above and below. Such an organic-inorganic composite hydrogel particle can be prepared using a temperature-sensitive monomer exhibiting LCST (lower critical solution temperature) in an aqueous solution as an organic monomer, for example, N-isopropylacrylamide. The resulting aqueous dispersion of hydrogel particles has an LCST temperature around 34 ° C., and at a higher temperature, for example 50 ° C., the aqueous dispersion becomes cloudy and the diameter of the spherical particles is 1/3 compared to 25 ° C. It became smaller. Application development to drug delivery system (DDS) is expected using the temperature responsiveness of hydrogel particles.

また、本発明のカルボン酸塩構造又はスルホン酸塩構造を有する有機無機複合ヒドロゲル粒子は水の中に大きく膨潤する性質を有する。例えば、ACMOとアクリル酸ナトリウムとの共重合で得られたヒドロゲル球状粒子は有機溶媒から水に分散させてから1時間経過すると、粒子径が約2倍に大きくなった。その優れた水膨潤性から、液吸収、増粘効果、結露防止、保水などの機能を利用した様々な用途に使用することができる。   Moreover, the organic-inorganic composite hydrogel particles having a carboxylate structure or a sulfonate structure of the present invention have a property of swelling greatly in water. For example, the hydrogel spherical particles obtained by copolymerization of ACMO and sodium acrylate had a particle size approximately doubled after 1 hour had passed since the organic solvent was dispersed in water. Due to its excellent water swellability, it can be used in various applications utilizing functions such as liquid absorption, thickening effect, prevention of condensation, and water retention.

また、本発明のジメチルアクリルアミド系の有機無機複合体粒子粉末は、ポリエチレングリコール(PEG)水溶液中で混ぜて製膜すると、ヒドロゲルフィルムを形成することができる。得られたゲルフィルムが優れた水膨潤性、力学物性及び透明性を有するため、創傷被覆材として用いられる。例えば、粒子粉末とPEG水溶液を混ぜて傷口を覆って、形成されたゲルフィルムは、傷口表面を細菌から保護し、傷口から出てくる侵出液を吸収し、かつ、乾いた創傷面にも湿潤環境を供与し、傷の痛みを軽減しつつ、治癒を促進することができる。また、化粧品分野でも、水分供給性(保水性)のある、人の皮膚に近い柔軟さを有する透明シートとしての展開が期待される。   Further, when the dimethylacrylamide-based organic / inorganic composite particle powder of the present invention is mixed in a polyethylene glycol (PEG) aqueous solution to form a film, a hydrogel film can be formed. Since the obtained gel film has excellent water swellability, mechanical properties and transparency, it is used as a wound dressing. For example, the gel film formed by mixing particle powder and PEG aqueous solution to cover the wound protects the wound surface from bacteria, absorbs the exudate emerging from the wound, and even on the dry wound surface Healing can be promoted while providing a moist environment and reducing wound pain. In the cosmetic field, it is expected to be developed as a transparent sheet having moisture supply property (water retention) and flexibility close to human skin.

本発明は、次の実施例によって更に具体的に説明する。なお、実施例中の部は重量部を表す。   The invention is further illustrated by the following examples. In addition, the part in an Example represents a weight part.

（測定）
＜偏光顕微鏡観察＞
有機無機複合ヒドロゲル粒子の水分散体をスライドガラスに乗せて、カバガラスを被せた後に、Nikon(株)製の偏光顕微鏡 ECLIPSE LV100POLを用いて、粒子形態及び粒子径を観測した。
各実施例、比較例に記載した粒子径は偏光顕微鏡観察により計測した値であり、任意の視野を写真撮影し、撮影された粒子の中から最小、最大と判断される粒子を選択し、その粒子径を計測した値である。
＜電子顕微鏡観察＞
粒子粉末試料を走査型電子顕微鏡用試料台の上で白金を用いて5nmの厚みに表面コートし、日立ハイテクノロジーズ社製の走査型電子顕微鏡(SEM) S-3400Nを用いて、粒子形態及び粒子径を観測した。
＜TG-DTA測定＞
有機無機複合ヒドロゲル粒子固形分中のクレイ含有率は、示差型熱質量分析装置(セイコー電子工業株式会社製TG-DTA220)を用いて、空気気流下、昇温速度10℃/分で、800℃まで焼成して測定した。
＜FT-IRの測定＞
フーリェ変換赤外吸収スペクトル(FT-IR)はジャスコエンジニアリング（株）製 FT-IR 4200を用い、4000cm-1〜400cm-1の範囲で測定を行った。
＜光透過率の測定＞
日本分光(株)製紫外可視分光光度計V-530を用いて、600nmの波長にて20℃〜50℃の範囲で光透過率の測定を行った。 (Measurement)
<Observation with polarizing microscope>
An aqueous dispersion of organic-inorganic composite hydrogel particles was placed on a slide glass and covered with a cover glass, and then the particle morphology and particle diameter were observed using a polarization microscope ECLIPSE LV100POL manufactured by Nikon Corporation.
The particle diameter described in each example and comparative example is a value measured by observation with a polarizing microscope, and an arbitrary field of view is photographed, and the particles judged to be the smallest and largest are selected from the photographed particles. This is a value obtained by measuring the particle diameter.
<Electron microscope observation>
The particle powder sample was surface coated with platinum on a scanning electron microscope sample stage to a thickness of 5 nm, and the particle morphology and particle size were measured using a scanning electron microscope (SEM) S-3400N manufactured by Hitachi High-Technologies Corporation. The diameter was observed.
<TG-DTA measurement>
The clay content in the organic-inorganic composite hydrogel particle solids is 800 ° C at a heating rate of 10 ° C / min under an air stream using a differential thermal mass spectrometer (TG-DTA220 manufactured by Seiko Denshi Kogyo Co., Ltd.). And calcined until measurement.
<Measurement of FT-IR>
Using Fourier transform infrared absorption spectrum (FT-IR) is Jusco Engineering Co. FT-IR 4200, was measured in a range of 4000cm -1 ~400cm -1.
<Measurement of light transmittance>
The light transmittance was measured in the range of 20 ° C. to 50 ° C. at a wavelength of 600 nm using a UV-visible spectrophotometer V-530 manufactured by JASCO Corporation.

(試薬)
・逆相懸濁重合溶媒
流パラ：流動パラフィン 試薬特級（和光純薬工業株式会社製）
シクロヘキサン 試薬特級（和光純薬工業株式会社製）
・界面活性剤
レオドールAO-10V（花王株式会社製）
・粘土鉱物
XLG：水膨潤性合成ヘクトライト（商標ラポナイトXLG、日本シリカ株式会社製）
XLＳ：6%ピロリン酸ナトリウム含有水膨潤性合成ヘクトライト（商標ラポナイトXLＳ、日本シリカ株式会社製）
・アルカリ
Na2CO3：炭酸ナトリウム（和光純薬工業株式会社製）
NaOH：粒状NaOH（和光純薬工業株式会社製）
・モノマー
DMAA：ジメチルアクリルアミド（和光純薬工業株式会社製）、活性アルミナを用いて重合禁止剤を取り除いてから使用した。
NIPAM：N-イソプロピルアクリルアミド（興人株式会社製）、トルエンとヘキサンの混合溶媒を用いて再結晶し無色針状結晶に精製してから用いた。
ACMO：アクリロイルモルフォリン（興人株式会社製）、活性アルミナを用いて重合禁止剤を取り除いてから使用した。
AAc：アクリル酸（和光純薬工業株式会社製）、試薬そのまま使用した。
AMPS：2-アクリルアミド-2-メチルプロパンスルホン酸（和光純薬工業株式会社製）、試薬そのまま使用した。
AAm：アクリルアミド（和光純薬工業株式会社製）、エタノールとヘキサンの混合溶媒を用いて再結晶し無色燐片状結晶に精製してから用いた。
MEA：2-メトキシエチルアクリレート（和光純薬工業株式会社製）、活性アルミナを用いて重合禁止剤を取り除いてから使用した。
AM-90G：CH2=CHCO(OC2H4)nOCH3 n=9 NKエステルAM-90G（新中村化学株式会社製）、試薬そのまま使用した。
AM-230G：CH2=CHCO(OC2H4)nOCH3 n=23 分子量1000 NKエステルAM-230G（新中村化学株式会社製）、試薬そのまま使用した。
M-450G：CH2=C(CH3)CO(OCH2CH2)nOCH3 n=45 分子量2000 NKエステルM-450G（新中村化学株式会社製）、試薬そのまま使用した。
M-900G：CH2=C(CH3)CO(OCH2CH2)nOCH3 n=90 分子量4000 NKエステルM-900G（新中村化学株式会社製）、試薬そのまま使用した。
・重合開始剤
KPS：ペルオキソ二硫酸カリウム（関東化学株式会社製）、KPS/水=0.2/10(g/g)の割合で純水で希釈し、水溶液にして使用した。
・重合触媒
TEMED：N,N,N’,N’-テトラメチルエチレンジアミン（和光純薬工業株式会社製） (reagent)
-Reversed phase suspension polymerization solvent flow para: liquid paraffin reagent special grade (manufactured by Wako Pure Chemical Industries, Ltd.)
Cyclohexane reagent special grade (Wako Pure Chemical Industries, Ltd.)
・ Surfactant Leodol AO-10V (manufactured by Kao Corporation)
・ Clay minerals
XLG: Water-swellable synthetic hectorite (Trademark Laponite XLG, manufactured by Nippon Silica Co., Ltd.)
XLS: Water-swelling synthetic hectorite containing 6% sodium pyrophosphate (Trademark Laponite XLS, manufactured by Nippon Silica Co., Ltd.)
·alkali
Na 2 CO 3 : Sodium carbonate (Wako Pure Chemical Industries, Ltd.)
NaOH: Granular NaOH (Wako Pure Chemical Industries, Ltd.)
·monomer
DMAA: Dimethylacrylamide (manufactured by Wako Pure Chemical Industries, Ltd.), activated alumina was used after removing the polymerization inhibitor.
NIPAM: N-isopropylacrylamide (manufactured by Kojin Co., Ltd.), recrystallized using a mixed solvent of toluene and hexane and purified into colorless needle crystals before use.
ACMO: Used after removing the polymerization inhibitor using acryloylmorpholine (manufactured by Kojin Co., Ltd.) and activated alumina.
AAc: Acrylic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and the reagent were used as they were.
AMPS: 2-acrylamido-2-methylpropanesulfonic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and the reagent were used as they were.
AAm: Acrylamide (manufactured by Wako Pure Chemical Industries, Ltd.), recrystallized using a mixed solvent of ethanol and hexane and purified to colorless flake crystals before use.
MEA: 2-methoxyethyl acrylate (Wako Pure Chemical Industries, Ltd.), activated alumina was used after removing the polymerization inhibitor.
AM-90G: CH 2 = CHCO (OC 2 H 4 ) nOCH 3 n = 9 NK ester AM-90G (manufactured by Shin-Nakamura Chemical Co., Ltd.), the reagent was used as it was.
AM-230G: CH 2 = CHCO (OC 2 H 4 ) nOCH 3 n = 23 Molecular weight 1000 NK ester AM-230G (manufactured by Shin-Nakamura Chemical Co., Ltd.), the reagent was used as it was.
M-450G: CH 2 ═C (CH 3 ) CO (OCH 2 CH 2 ) nOCH 3 n = 45 Molecular weight 2000 NK ester M-450G (manufactured by Shin-Nakamura Chemical Co., Ltd.), the reagent was used as it was.
M-900G: CH 2 = C (CH 3 ) CO (OCH 2 CH 2 ) nOCH 3 n = 90 Molecular weight 4000 NK ester M-900G (manufactured by Shin-Nakamura Chemical Co., Ltd.), the reagent was used as it was.
・ Polymerization initiator
KPS: Potassium peroxodisulfate (manufactured by Kanto Chemical Co., Inc.), diluted with pure water at a ratio of KPS / water = 0.2 / 10 (g / g) and used as an aqueous solution.
・ Polymerization catalyst
TEMED: N, N, N ', N'-tetramethylethylenediamine (Wako Pure Chemical Industries, Ltd.)

(実施例1)
流動パラフィン30部に界面活性剤レオドールAO-10V 0.3部を攪拌して溶解させた。次に、25分間窒素パブリングし、更に氷浴で冷やして油相(連続相)とする。一方、表1に示した処方に基づいて、平底ガラス容器に、純水19部を攪拌しながら、0.8部のＸＬＧを添加して無色透明の溶液を調製した。これにDMAA2部を加え、15分間窒素バブリングした。続いて、氷浴下、TEMED 0.016部、ＫＰＳ水溶液1部を順次攪拌して加え、均一溶液である水相(分散相)を得た。得られた水相から速やかに2.5部を採取して攪拌している油相に加えた。溶液は白濁になり、25℃、12時間攪拌反応させてＷ／Ｏ型エマルジョンを得た。このエマルジョンに10部の水を添加混合した後、遠心分離によりヒドロゲル粒子を沈降させた。上澄みを除き、等量のヘキサン/水混合溶媒で遠心分離により粒子を二回洗浄した。得られた粒子を水に分散し、偏光顕微鏡観察を行った。図1に示したように粒子形態はほぼ真球の球状粒子で、粒径が5〜56μmであった。また、粒子の水分散体を乾燥して固形分の収率が64%であった。なお、乾燥粒子のＴＧ−ＤＴＡを測定したところ、灰分（クレイ）が25%であり、仕込み組成とほぼ一致した。これらの分析結果を表８にまとめて示す。 (Example 1)
In 30 parts of liquid paraffin, 0.3 part of the surfactant Leodol AO-10V was stirred and dissolved. Next, nitrogen publishing is performed for 25 minutes, followed by cooling in an ice bath to obtain an oil phase (continuous phase). On the other hand, based on the formulation shown in Table 1, 0.8 parts of XLG was added to a flat bottom glass container while stirring 19 parts of pure water to prepare a colorless and transparent solution. To this, 2 parts of DMAA was added and nitrogen bubbling was performed for 15 minutes. Subsequently, 0.016 parts of TEMED and 1 part of an aqueous KPS solution were sequentially added in an ice bath to obtain an aqueous phase (dispersed phase) as a homogeneous solution. 2.5 parts were quickly collected from the obtained aqueous phase and added to the stirring oil phase. The solution became cloudy and was stirred and reacted at 25 ° C. for 12 hours to obtain a W / O type emulsion. After adding 10 parts of water to the emulsion and mixing, hydrogel particles were precipitated by centrifugation. The supernatant was removed and the particles were washed twice by centrifugation with an equal volume of hexane / water mixed solvent. The obtained particles were dispersed in water and observed with a polarizing microscope. As shown in FIG. 1, the particle morphology was almost spherical particles with a particle size of 5 to 56 μm. Further, the aqueous dispersion of particles was dried, and the yield of solid content was 64%. When TG-DTA of the dried particles was measured, the ash content (clay) was 25%, which almost coincided with the charged composition. The results of these analyzes are summarized in Table 8.

（実施例2〜9）
表1,2に示した分散相組成及び表8,9,10に示した連続相組成と重合条件で、実施例1と同様な添加順序でそれぞれのヒドロゲル粒子を合成した。また、実施例1と同様にして粒子を精製し、その水分散体を調製した。得られたヒドロゲル粒子の収率、粒子径及び固形分の灰分(クレイ)を表8,9,10にまとめて示す。界面活性剤の少ない実施例3,9に対して、界面活性剤の多い実施例2,8で得られた粒子が小さいことがわかった。また、シクロヘキサンを用いた実施例4,6の粒子は流動パラフィンを用いた実施例3,5より大きいことを示された。なお、実施例2,4,5,6,7,8のヒドロゲル粒子の水分散体の偏光顕微鏡写真を図2〜7に示す。
また、実施例7で得られたヒドロゲル粒子の水分散体の光透過率の温度依存性を測定したところ、図20に示したように35℃付近に光透過率は急激に低下することを示し、LCSTを有することが明らかである。一方、実施例7の水分散体を室温(25℃)で一週間放置し、平衡膨潤度に達した粒子の粒径を測り、7〜30μmであった。次に、この水分散体を50℃にして、粒子径を再び測ると、3〜15μmになり、明確な温度応答性を示した。 (Examples 2 to 9)
Each hydrogel particle was synthesized in the same order of addition as in Example 1, with the dispersed phase composition shown in Tables 1 and 2 and the continuous phase composition and polymerization conditions shown in Tables 8, 9, and 10. Further, the particles were purified in the same manner as in Example 1 to prepare an aqueous dispersion. The yield, particle diameter, and solid ash (clay) of the obtained hydrogel particles are summarized in Tables 8, 9, and 10. It was found that the particles obtained in Examples 2 and 8 with a large amount of surfactant were smaller than those in Examples 3 and 9 with a small amount of surfactant. It was also shown that the particles of Examples 4 and 6 using cyclohexane were larger than Examples 3 and 5 using liquid paraffin. In addition, the polarization micrographs of the aqueous dispersions of hydrogel particles of Examples 2, 4, 5, 6, 7, and 8 are shown in FIGS.
Further, when the temperature dependence of the light transmittance of the aqueous dispersion of hydrogel particles obtained in Example 7 was measured, it was shown that the light transmittance sharply decreased around 35 ° C. as shown in FIG. It is clear to have LCST. On the other hand, the aqueous dispersion of Example 7 was allowed to stand at room temperature (25 ° C.) for one week, and the particle size of the particles that reached the equilibrium swelling degree was measured and found to be 7 to 30 μm. Next, when this aqueous dispersion was brought to 50 ° C. and the particle diameter was measured again, it became 3 to 15 μm, and a clear temperature response was exhibited.

(実施例10)
流動パラフィン30部に界面活性剤レオドールAO-10V 0.2部を攪拌して溶解させた。次に、25分間窒素パブリングし、更に氷浴で冷やして油相(連続相)とする。一方、表3に示した処方に基づいて、平底ガラス容器に、純水19部を攪拌しながら、0.8部のＸＬＳを添加して無色透明の溶液を調製した。これにDMAA1.8部を加え、15分間窒素バブリングした。続いて、氷浴下、ＫＰＳ水溶液1部を添加した直後に、DMAEA 0.2部、Ｈ２Ｏ 1部及びTEMED 0.016部の混合溶液を攪拌して加え、均一溶液である水相(分散相)を得た。得られた水相から速やかに2.5部を採取して攪拌している油相に加えた。溶液は白濁になり、25℃、12時間攪拌反応させてＷ／Ｏ型エマルジョンを得た。また、水の代わりに0.9%食塩水を用いた以外に実施例1と同様にヒドロゲル粒子を分離精製し、その食塩水分散体を調製した。得られたヒドロゲル粒子の収率、粒子径及び固形分の灰分を表11に示す。 (Example 10)
In 30 parts of liquid paraffin, 0.2 part of the surfactant Leodol AO-10V was stirred and dissolved. Next, nitrogen publishing is performed for 25 minutes, followed by cooling in an ice bath to obtain an oil phase (continuous phase). On the other hand, based on the formulation shown in Table 3, 0.8 parts of XLS was added to a flat bottom glass container while stirring 19 parts of pure water to prepare a colorless and transparent solution. To this, 1.8 parts of DMAA was added and nitrogen bubbling was performed for 15 minutes. Subsequently, immediately after adding 1 part of the KPS aqueous solution in an ice bath, a mixed solution of 0.2 part of DMAEA, 1 part of H 2 O and 0.016 part of TEMED was added with stirring, and an aqueous phase (dispersed phase) as a homogeneous solution was added. Obtained. 2.5 parts were quickly collected from the obtained aqueous phase and added to the stirring oil phase. The solution became cloudy and was stirred and reacted at 25 ° C. for 12 hours to obtain a W / O type emulsion. Further, hydrogel particles were separated and purified in the same manner as in Example 1 except that 0.9% saline was used instead of water, and a saline dispersion was prepared. Table 11 shows the yield, particle size, and solid ash content of the obtained hydrogel particles.

(実施例11〜15,17)
表4,5に示した分散相組成及び表11,12,13に示した連続相組成と重合条件で、DMAEAの代わりにアクリル酸と炭酸ナトリウムとの中和物水溶液を用いて、実施例10と同様な添加順序でそれぞれのヒドロゲル粒子を合成した。また、実施例11〜15は、実施例10と同様にして粒子を精製し、その食塩水分散体を調製した。得られたヒドロゲル粒子の収率、粒子径及び固形分灰分を表11,12,13にまとめて示す。これらに対して、実施例17は、食塩水の代わりに純水を用いて粒子を精製した結果、粒子が大きく膨潤して粒子径800μmを超えた球状粒子も観察された。また、実施例14で得られたヒドロゲル粒子乾燥物のFT-IRスペクトルを測定したところ、図21に示したように1580cm-1にCOONaに由来するピークが観測された。なお、実施例12,14,17のヒドロゲル粒子の食塩水分散体又は水分散体の偏光顕微鏡写真を図8,9,10に示す。
一方、実施例15で得られたヒドロゲル粒子は、食塩水の代わりに水を用い、粒子の水分散体を調製した直後、粒径が20〜161μmであった。この粒子の水分散体を1時間放置したところ、粒子が大きく膨潤し、粒径が35〜278μmになった。このことから、カルボン酸塩構造を有するヒドロゲル粒子の水膨潤性が極めて優れていることがわかった。 (Examples 11-15, 17)
A dispersion phase composition shown in Tables 4 and 5 and a continuous phase composition and polymerization conditions shown in Tables 11, 12, and 13 were used except that a neutralized aqueous solution of acrylic acid and sodium carbonate was used instead of DMAEA. Each hydrogel particle was synthesized in the same order of addition. In Examples 11 to 15, particles were purified in the same manner as in Example 10 to prepare a saline dispersion. Tables 11, 12, and 13 collectively show the yield, particle size, and solid ash content of the obtained hydrogel particles. On the other hand, in Example 17, as a result of purifying particles using pure water instead of saline, spherical particles having a particle size exceeding 800 μm due to large swelling were observed. Further, when the FT-IR spectrum of the dried hydrogel particles obtained in Example 14 was measured, a peak derived from COONa was observed at 1580 cm −1 as shown in FIG. In addition, the polarization micrographs of the saline dispersion or the aqueous dispersion of the hydrogel particles of Examples 12, 14, and 17 are shown in FIGS.
On the other hand, the hydrogel particles obtained in Example 15 had a particle size of 20 to 161 μm immediately after preparing an aqueous dispersion of particles using water instead of saline. When the aqueous dispersion of the particles was allowed to stand for 1 hour, the particles swelled greatly and the particle size became 35 to 278 μm. From this, it was found that the water swellability of hydrogel particles having a carboxylate structure is extremely excellent.

(実施例16)
実施例15で得られたカルポン酸塩構造を有するヒドロゲル粒子の水分散体は、遠心分離によって水を除き、0.1N塩酸を28部添加し、25℃で8時間攪拌した。偏光顕微鏡を観察したところ、粒子形態は変化せず、粒径が15〜143μmであった。この粒子の酸性水分散体を遠心分離により水洗浄を行った後、熱風乾燥させた。得られたヒドロゲル粒子の固形分収率が55%であった。また、乾燥物のFT-IRスペクトルを測定したところ、図22に示したように1580cm-1のCOONaに由来するピークが消失し、新たに1730cm-1のCOOHに由来するピークが観測された。酸処理することによりCOONaをCOOHに変換し、カルボキシル基を有するヒドロゲル粒子が得られることがわかった。 (Example 16)
The aqueous dispersion of hydrogel particles having a carboxylate structure obtained in Example 15 was freed of water by centrifugation, added with 28 parts of 0.1N hydrochloric acid, and stirred at 25 ° C. for 8 hours. When a polarizing microscope was observed, the particle morphology did not change and the particle size was 15 to 143 μm. The acidic aqueous dispersion of the particles was washed with water by centrifugation and then dried with hot air. The solid content yield of the obtained hydrogel particles was 55%. Further, when the FT-IR spectrum of the dried product was measured, as shown in FIG. 22, the peak derived from 1580 cm −1 COONa disappeared, and a new peak derived from 1730 cm −1 COOH was observed. It was found that hydrogel particles having a carboxyl group can be obtained by converting COONa to COOH by acid treatment.

(実施例18)
表4に示した分散相組成及び表13に示した連続相組成と重合条件で、DMAEAの代わりに2-アクリルアミド-2-メチルプロパンスルホン酸と炭酸ナトリウムとの中和物水溶液を用いて、実施例10と同様な添加順序でヒドロゲル粒子を合成した。次に実施例1と同様にヒドロゲル粒子を分離精製し、その水分散体を調製した。得られたヒドロゲル粒子の収率、粒子径及び固形分の灰分を表13に示す。図11にも示したように、水の中にヒドロゲル粒子が大きく膨潤し、粒子径1000μmの大粒子も観測された。このことから、スルホン酸塩構造を有するヒドロゲル粒子の水膨潤性が極めて優れていることが明らかになった。 (Example 18)
Conducted by using a neutralized aqueous solution of 2-acrylamido-2-methylpropanesulfonic acid and sodium carbonate in place of DMAEA with the dispersed phase composition shown in Table 4 and the continuous phase composition and polymerization conditions shown in Table 13. Hydrogel particles were synthesized in the same order of addition as in Example 10. Next, hydrogel particles were separated and purified in the same manner as in Example 1 to prepare an aqueous dispersion. Table 13 shows the yield, particle diameter, and solid ash content of the obtained hydrogel particles. As shown in FIG. 11, hydrogel particles swelled greatly in water, and large particles with a particle size of 1000 μm were also observed. From this, it was revealed that the water swellability of hydrogel particles having a sulfonate structure is extremely excellent.

(実施例19〜21)
表3に示した分散相組成及び表14に示した連続相組成と重合条件で、実施例1と同様な添加順序でそれぞれのヒドロゲル粒子を合成した。また、実施例1と同様にして粒子を精製し、その水分散体を調製した。得られたヒドロゲル粒子の収率、粒子径及び固形分の灰分を表14にまとめて示す。なお、実施例19,21のヒドロゲル粒子の水分散体の偏光顕微鏡写真を図12,13に示す。 (Examples 19 to 21)
Each hydrogel particle was synthesized in the same order of addition as in Example 1, with the dispersed phase composition shown in Table 3, the continuous phase composition shown in Table 14, and the polymerization conditions. Further, the particles were purified in the same manner as in Example 1 to prepare an aqueous dispersion. Table 14 summarizes the yield, particle size, and solid ash content of the resulting hydrogel particles. Polarized micrographs of the aqueous dispersions of hydrogel particles of Examples 19 and 21 are shown in FIGS.

(実施例22)
実施例21で得られたヒドロゲル粒子の水分散体20部に水酸化ナトリウム0.5部を添加し、溶解させた。この溶液を60℃、10時間加熱処理することによって、粒子の高分子鎖にアクリルアミドユニットのアミド基が加水分解され、カルポン酸ナトリウムに変換された。次に1N塩酸水溶液で過剰の水酸化ナトリウムを中和し、カルボン酸塩構造を有するヒドロゲル粒子の食塩水分散体を得た。偏光顕微鏡で観測したところ、粒子径が4〜50μmであった。また、このヒドロゲル粒子の乾燥体のFT-IRスペクトルを測定したところ、図23に示したように1580cm-1にCOONaに由来するピークが確認された。一方、得られたヒドロゲル粒子の食塩水分散体を大量の純水の中で三日間透析を行い、食塩を除去したところ、粒子径が16〜136μmになり、大きく膨潤することがわかった。 (Example 22)
To 20 parts of the aqueous dispersion of hydrogel particles obtained in Example 21, 0.5 part of sodium hydroxide was added and dissolved. By heat-treating this solution at 60 ° C. for 10 hours, the amide group of the acrylamide unit was hydrolyzed into the polymer chains of the particles and converted to sodium carboxylic acid. Next, excess sodium hydroxide was neutralized with a 1N aqueous hydrochloric acid solution to obtain a saline dispersion of hydrogel particles having a carboxylate structure. When observed with a polarizing microscope, the particle size was 4 to 50 μm. Further, when the FT-IR spectrum of the dried product of the hydrogel particles was measured, a peak derived from COONa was confirmed at 1580 cm −1 as shown in FIG. On the other hand, when the salt dispersion of the obtained hydrogel particles was dialyzed in a large amount of pure water for 3 days to remove the salt, it was found that the particle diameter became 16 to 136 μm and swollen greatly.

(実施例23〜26)
式1で表されるアクリルモノマーを用いて、表6及び表7に示した分散相組成と表15に示した連続相組成及び重合条件で、実施例1と同様な添加順序でそれぞれのヒドロゲル粒子を合成した。また、実施例1と同様にして粒子を精製し、その水分散体を調製した。得られたヒドロゲル粒子の収率、粒子径及び固形分の灰分を表15にまとめて示す。また、実施例23のヒドロゲル粒子の乾燥物のFT-IRスペクトルを測定したところ、図24に示したように1730cm-1にAM-90Gのカルボニルに由来するピークが観測された。なお、実施例23,24,25,26のヒドロゲル粒子の水分散体の偏光顕微鏡写真をそれぞれ図14,15,16,17に示す。 (Examples 23 to 26)
Using the acrylic monomer represented by Formula 1, each hydrogel particle in the same order of addition as in Example 1 with the dispersed phase composition shown in Tables 6 and 7 and the continuous phase composition and polymerization conditions shown in Table 15 Was synthesized. Further, the particles were purified in the same manner as in Example 1 to prepare an aqueous dispersion. Table 15 summarizes the yield, particle diameter, and solid ash content of the obtained hydrogel particles. Further, when the FT-IR spectrum of the dried hydrogel particles of Example 23 was measured, a peak derived from AM-90G carbonyl was observed at 1730 cm −1 as shown in FIG. In addition, the polarization micrographs of the aqueous dispersions of the hydrogel particles of Examples 23, 24, 25, and 26 are shown in FIGS. 14, 15, 16, and 17, respectively.

(実施例27)
流動パラフィン30部に界面活性剤レオドールAO-10V 0.3部を攪拌して溶解させた。次に、25分間窒素パブリングし、更に氷浴で冷やして油相(連続相)とする。一方、表7に示した処方に基づいて、平底ガラス容器に、純水18部を攪拌しながら、1.6部のＸＬＳを添加して無色透明の溶液を調製した。これにDMAA 1.7部とAM-230G 0.2部を加え、15分間窒素バブリングした。続いて、氷浴下、ＫＰＳ水溶液1部を添加した直後に、ＡＡｃ 0.1部、炭酸ナトリウム0.09部、H2O 1部及びTEMED 0.016部の混合溶液を攪拌して加え、均一溶液である水相(分散相)を得た。得られた水相から速やかに2.5部を採取して攪拌している油相に加えた。溶液は白濁になり、25℃、12時間攪拌反応させてＷ／Ｏ型エマルジョンを得た。また、水の代わりに0.9%食塩水を用いた以外に実施例1と同様にヒドロゲル粒子を分離精製し、その食塩水分散体を調製した。次に、遠心分離によって粒子を回収し、純水で三回洗浄して、食塩を除いたヒドロゲル粒子の水分散体を得た。図18と図19に示したように、水中のヒドロゲル粒子は食塩水中より粒子径が大きくなった。カルボン酸基導入することによってヒドロゲル粒子の水膨潤性が大幅に向上したことがわかった。また、得られたヒドロゲル粒子の収率、粒子径及び固形分の灰分を表16に示す。 (Example 27)
In 30 parts of liquid paraffin, 0.3 part of the surfactant Leodol AO-10V was stirred and dissolved. Next, nitrogen publishing is performed for 25 minutes, followed by cooling in an ice bath to obtain an oil phase (continuous phase). On the other hand, based on the formulation shown in Table 7, 1.6 parts of XLS was added to a flat bottom glass container while stirring 18 parts of pure water to prepare a colorless and transparent solution. To this, 1.7 parts of DMAA and 0.2 part of AM-230G were added, and nitrogen bubbling was performed for 15 minutes. Subsequently, immediately after adding 1 part of an aqueous KPS solution in an ice bath, a mixed solution of 0.1 part of AAc, 0.09 part of sodium carbonate, 1 part of H2O and 0.016 part of TEMED was added with stirring, and an aqueous phase (dispersion) was obtained. Phase). 2.5 parts were quickly collected from the obtained aqueous phase and added to the stirring oil phase. The solution became cloudy and was stirred and reacted at 25 ° C. for 12 hours to obtain a W / O type emulsion. Further, hydrogel particles were separated and purified in the same manner as in Example 1 except that 0.9% saline was used instead of water, and a saline dispersion was prepared. Next, the particles were collected by centrifugation and washed three times with pure water to obtain an aqueous dispersion of hydrogel particles excluding salt. As shown in FIGS. 18 and 19, the hydrogel particles in water had a larger particle size than that in saline. It was found that the water swellability of the hydrogel particles was greatly improved by introducing the carboxylic acid group. Table 16 shows the yield, particle diameter, and solid ash content of the obtained hydrogel particles.

(実施例28)
表1に示した分散相組成及び表17に示した連続相組成と重合条件で、実施例1と同様な添加順序でW/O型エマルジョンを合成した。次に遠心分離でエマルジョンの中のヒドロゲル粒子を沈降させ、デカンテーションで上澄みを除いた。続いて、アセトンで3回繰り返してヒドロゲル粒子を洗浄し、粒子中の水分を除去した。得られた粒子粉末を50℃熱風乾燥し、収率は84%であった。SEMで観察したところ、一次粒子径は2〜16μmであった(図25)。なお、粒子粉末のＴＧ−ＤＴＡを測定したところ、灰分（クレイ）が30%であった。これらの分析結果を表１７にまとめて示す。 (Example 28)
A W / O emulsion was synthesized in the same order of addition as in Example 1 with the dispersion phase composition shown in Table 1 and the continuous phase composition and polymerization conditions shown in Table 17. Next, the hydrogel particles in the emulsion were sedimented by centrifugation, and the supernatant was removed by decantation. Subsequently, the hydrogel particles were washed three times with acetone to remove moisture in the particles. The obtained particle powder was dried with hot air at 50 ° C., and the yield was 84%. When observed by SEM, the primary particle size was 2 to 16 μm (FIG. 25). In addition, when TG-DTA of particle powder was measured, ash (clay) was 30%. These analysis results are summarized in Table 17.

（比較例1）
表1に示した実施例１の分散相処方D-NC5に基づいて、平底ガラス容器に、純水19部を攪拌しながら、0.8部のＸＬＧを添加して無色透明の溶液を調製した。これにDMAA 2部を加え、15分間窒素バブリングした。続いて、氷浴下、TEMED 0.016部、ＫＰＳ水溶液1部を順次攪拌して加え、20℃にて12時間靜置重合を行い、透明な伸縮性のあるヒドロゲルが得られた。このヒドロゲルを乾燥し、ミキサで粉砕することによって乾燥ゲル粉末を得た。SEMで観察したところ、粒子径180μm前後の無定形粒子であった(図26)。 (Comparative Example 1)
Based on the dispersed phase formulation D-NC5 of Example 1 shown in Table 1, 0.8 part of XLG was added to a flat bottom glass container while stirring 19 parts of pure water to prepare a colorless and transparent solution. To this was added 2 parts of DMAA and nitrogen bubbling was performed for 15 minutes. Subsequently, 0.016 parts of TEMED and 1 part of an aqueous KPS solution were sequentially stirred and added in an ice bath, and in situ polymerization was carried out at 20 ° C. for 12 hours to obtain a transparent stretchable hydrogel. The hydrogel was dried and pulverized with a mixer to obtain a dry gel powder. Observation by SEM revealed amorphous particles with a particle size of around 180 μm (FIG. 26).

(実施例29〜31)
表1に示した分散相組成及び表17,18に示した連続相組成と重合条件で、実施例28と同様にしてW/O型エマルジョンを合成し、アセトン洗浄によって粒子粉末を得た。分析結果を表17,18にまとめて示す。表に示したようにシクロヘキサンを用いて合成した粒子は流動パラフィンを用いた場合と比べて粒子径が大きくなった。 (Examples 29 to 31)
A W / O emulsion was synthesized in the same manner as in Example 28 with the dispersed phase composition shown in Table 1 and the continuous phase composition and polymerization conditions shown in Tables 17 and 18, and particle powder was obtained by washing with acetone. The analysis results are summarized in Tables 17 and 18. As shown in the table, the particles synthesized using cyclohexane had a larger particle size than those using liquid paraffin.

(応用例1)
実施例28,29,30,31で得られた粒子粉末3部に、分子量4,000のポリエチレングリコール(PEG)の1%水溶液18部を加え、かき混ぜた後、基材に延ばして製膜した。37℃で30分静置することによって粒子がお互い融着し、一体化したヒドロゲルフィルムを形成した。このゲルフィルムは優れた水膨潤性と力学物性を有するため、創傷被覆材として用いられる。 (Application 1)
18 parts of a 1% aqueous solution of polyethylene glycol (PEG) having a molecular weight of 4,000 was added to 3 parts of the particle powders obtained in Examples 28, 29, 30, and 31, and the mixture was stirred and then extended to a substrate to form a film. The particles were fused with each other by standing at 37 ° C. for 30 minutes to form an integrated hydrogel film. Since this gel film has excellent water swellability and mechanical properties, it is used as a wound dressing.

(実施例32,33)
表1,2に示した分散相組成及び表18に示した連続相組成と重合条件で、実施例28と同様にしてW/O型エマルジョンを合成した。次に実施例28と同様にアセトン洗浄を行い、更にヘキサンで2回洗浄した。得られた粒子粉末の分析結果を表18にまとめて示す。なお、実施例32で得られた粒子のSEM写真を図28に示す。 (Examples 32 and 33)
A W / O type emulsion was synthesized in the same manner as in Example 28 with the dispersed phase composition shown in Tables 1 and 2 and the continuous phase composition and polymerization conditions shown in Table 18. Next, acetone was washed in the same manner as in Example 28, and further washed twice with hexane. The analysis results of the obtained particle powder are summarized in Table 18. An SEM photograph of the particles obtained in Example 32 is shown in FIG.

(実施例34)
流動パラフィン30部に界面活性剤レオドールAO-10V 0.3部を攪拌して溶解させた。次に、25分間窒素パブリングし、更に氷浴で冷やして油相(連続相)とする。一方、表4に示した処方に基づいて、平底ガラス容器に、純水16部を攪拌しながら、0.8部のXLSを添加して無色透明の溶液を調製した。これにDMAA 1.2部を加え、15分間窒素バブリングした。続いて、氷浴下、KPS水溶液1部を添加した直後に、AAc 0.8部、炭酸ナトリウム0.66部、H2O 3部及びTEMED 0.016部の混合溶液を攪拌して加え、均一溶液である水相(分散相)を得た。得られた水相から速やかに2.5部を採取して攪拌している油相に加えた。溶液は白濁になり、25℃、12時間攪拌反応させてW/O型エマルジョンを得た。次に実施例28と同様にヒドロゲル粒子を分離し、アセトン洗浄によって粒子粉末を得た。得られた粒子粉末の収率、粒子径及び灰分を表19と図29に示す。 (Example 34)
In 30 parts of liquid paraffin, 0.3 part of the surfactant Leodol AO-10V was stirred and dissolved. Next, nitrogen publishing is performed for 25 minutes, followed by cooling in an ice bath to obtain an oil phase (continuous phase). On the other hand, based on the formulation shown in Table 4, 0.8 parts of XLS was added to a flat bottom glass container while stirring 16 parts of pure water to prepare a colorless and transparent solution. To this, 1.2 parts of DMAA was added, and nitrogen was bubbled for 15 minutes. Subsequently, immediately after adding 1 part of KPS aqueous solution in an ice bath, a mixed solution of 0.8 part of AAc, 0.66 part of sodium carbonate, 3 parts of H2O and 0.016 part of TEMED was added with stirring, and the aqueous phase (dispersion) was a uniform solution. Phase). 2.5 parts were quickly collected from the obtained aqueous phase and added to the stirring oil phase. The solution became cloudy and was stirred and reacted at 25 ° C. for 12 hours to obtain a W / O type emulsion. Next, hydrogel particles were separated in the same manner as in Example 28, and particle powder was obtained by washing with acetone. The yield, particle diameter, and ash content of the obtained particle powder are shown in Table 19 and FIG.

(実施例35)
表5に示した分散相組成及び表19に示した連続相組成と重合条件で、DMAAの代わりにACMOを用いて実施例34と同様にして粒子粉末を得た。分析結果を表19に示す。 (Example 35)
Particle powder was obtained in the same manner as in Example 34 using ACMO instead of DMAA with the dispersed phase composition shown in Table 5 and the continuous phase composition and polymerization conditions shown in Table 19. The analysis results are shown in Table 19.

(実施例36)
表4に示した分散相組成及び表19に示した連続相組成と重合条件で、AAcの代わりにAMPSを用いて実施例34と同様にして粒子粉末を得た。分析結果を表19に示す。 Example 36
Particle powder was obtained in the same manner as in Example 34 using AMPS instead of AAc with the dispersion phase composition shown in Table 4 and the continuous phase composition and polymerization conditions shown in Table 19. The analysis results are shown in Table 19.

(実施例37)
表6に示した分散相組成及び表20に示した連続相組成と重合条件で、実施例28と同様にしてW/O型エマルジョンを合成し、アセトン洗浄によってPEG側鎖を有する粒子粉末を得た。得られた粒子粉末の収率、粒子径及び灰分を表20と図30に示す。 (Example 37)
Using the dispersed phase composition shown in Table 6 and the continuous phase composition and polymerization conditions shown in Table 20, a W / O emulsion was synthesized in the same manner as in Example 28, and a particle powder having PEG side chains was obtained by washing with acetone. It was. The yield, particle diameter and ash content of the obtained particle powder are shown in Table 20 and FIG.

(実施例38)
表1に示した分散相組成及び表20に示した連続相組成と重合条件で、実施例1と同様に
W/O型エマルジョンを合成した。次にエマルジョンを攪拌しながら、90℃で3時間加熱することによってヒドロゲル粒子中の水分を除いた。遠心分離で回収した粒子をヘキサンで二回洗浄し、乾燥することによって粒子粉末を得た。偏光顕微鏡で観察したところ、粒子径2〜20μmの球状粒子とその凝集体であることがわかった(図31)。また、粒子断面のSEM観察から球状粒子の一部は中空状球状粒子であることが明らかになった(図32)。他の分析結果を表20に示す。 (Example 38)
As in Example 1, with the dispersed phase composition shown in Table 1 and the continuous phase composition and polymerization conditions shown in Table 20.
A W / O type emulsion was synthesized. Next, the water in the hydrogel particles was removed by heating the emulsion at 90 ° C. for 3 hours while stirring. The particles collected by centrifugation were washed twice with hexane and dried to obtain particle powder. Observation with a polarizing microscope revealed spherical particles having a particle diameter of 2 to 20 μm and aggregates thereof (FIG. 31). In addition, SEM observation of the particle cross section revealed that some of the spherical particles were hollow spherical particles (FIG. 32). Other analysis results are shown in Table 20.

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Figure 2011012107
Figure 2011012107

Claims (12)

(メタ)アクリルアミド類を含むモノマーを重合した水溶性有機高分子(A)と、水膨潤性粘土鉱物(B)とが複合化して形成された三次元網目の中に水(C)が包含されている有機無機複合体ヒドロゲル粒子。 Water (C) is included in a three-dimensional network formed by combining a water-soluble organic polymer (A) obtained by polymerizing monomers containing (meth) acrylamides and a water-swellable clay mineral (B). Organic-inorganic composite hydrogel particles. 粒子の形状が球形である請求項１記載の有機無機複合体ヒドロゲル粒子。 The organic-inorganic composite hydrogel particle according to claim 1, wherein the particle has a spherical shape. アミノ基、カルボン酸基、カルボン酸塩構造の基、スルホン酸基又はスルホン酸塩構造の基を有する請求項１又は２記載の有機無機複合体ヒドロゲル粒子。 The organic-inorganic composite hydrogel particle according to claim 1 or 2, which has an amino group, a carboxylic acid group, a carboxylate structure group, a sulfonic acid group or a sulfonate structure group. 前記水溶性有機高分子(A)が、(メタ)アクリルアミド類と式（１）で表されるモノマーの重合体である請求項1又は2記載の有機無機複合体ヒドロゲル粒子。
Figure 2011012107
 （式中、Ｒ１は、水素原子又はメチル基、Ｒ２は炭素数２又は３のアルキレン基、ｎは3〜９９の整数、Ｙはメトキシ基又は水酸基を表す。） 3. The organic-inorganic composite hydrogel particle according to claim 1, wherein the water-soluble organic polymer (A) is a polymer of (meth) acrylamides and a monomer represented by the formula (1).
Figure 2011012107
 (Wherein R 1 represents a hydrogen atom or a methyl group, R 2 represents an alkylene group having 2 or 3 carbon atoms, n represents an integer of 3 to 99, and Y represents a methoxy group or a hydroxyl group.) 請求項１〜４のいずれかに記載の有機無機複合体ヒドロゲル粒子が水中に分散した水分散体。 An aqueous dispersion in which the organic-inorganic composite hydrogel particles according to claim 1 are dispersed in water. 請求項１〜４のいずれかに記載の有機無機複合体ヒドロゲル粒子から水を除去した有機無機複合体粒子。 Organic / inorganic composite particles obtained by removing water from the organic / inorganic composite hydrogel particles according to claim 1. 中空状粒子である請求項６記載の有機無機複合体粒子。 The organic-inorganic composite particle according to claim 6, which is a hollow particle. 水膨潤性粘土鉱物(B)と(メタ)アクリルアミド類を含むモノマーと水(C)を含む分散相を製造し、該分散相を疎水性分散媒(D)及び界面活性剤(E)を含む連続相と混合し、次いで該モノマーを逆相懸濁重合させることによりW/O型エマルジョンを製造する工程を含む請求項１〜４のいずれかに記載の有機無機複合体ヒドロゲル粒子の製造方法。 A water-swellable clay mineral (B), a monomer containing (meth) acrylamides and a dispersed phase containing water (C) are produced, and the dispersed phase contains a hydrophobic dispersion medium (D) and a surfactant (E). The method for producing organic-inorganic composite hydrogel particles according to any one of claims 1 to 4, comprising a step of producing a W / O emulsion by mixing with a continuous phase and then subjecting the monomer to reverse phase suspension polymerization. 前記界面活性剤(E)がソルビタン脂肪酸エステルである請求項８記載の有機無機複合体ヒドロゲル粒子の製造方法。 The method for producing organic-inorganic composite hydrogel particles according to claim 8, wherein the surfactant (E) is sorbitan fatty acid ester. 水膨潤性粘土鉱物(B)と(メタ)アクリルアミド類を含むモノマーと水(C)を含む分散相を製造し、該分散相を疎水性分散媒(D)及び界面活性剤(E)を含む連続相と混合し、次いで該モノマーを逆相懸濁重合させることによりW/O型エマルジョンを製造し、その後、W/O型エマルジョン中の水(C)を除去する工程を含む請求項６記載の有機無機複合体粒子の製造方法。 A water-swellable clay mineral (B), a monomer containing (meth) acrylamides and a dispersed phase containing water (C) are produced, and the dispersed phase contains a hydrophobic dispersion medium (D) and a surfactant (E). 7. A step of preparing a W / O emulsion by mixing with a continuous phase and then subjecting the monomer to reverse phase suspension polymerization, and then removing water (C) in the W / O emulsion. The manufacturing method of organic-inorganic composite particle | grains of this. 前記W/O型エマルジョン中の水（C）を除去する工程が、水と相溶する有機溶媒で水(C)を置換する工程を含む請求項１０記載の有機無機複合体粒子の製造方法。 The method for producing organic-inorganic composite particles according to claim 10, wherein the step of removing water (C) in the W / O emulsion includes a step of replacing water (C) with an organic solvent compatible with water. 前記疎水性分散媒(D)の沸点が水の沸点以上であり、前記W/O型エマルジョン中の水（C）を除去する工程が、前記W/O型エマルジョンを加熱する操作を含む請求項１０記載の有機無機複合体粒子の製造方法。 The boiling point of the hydrophobic dispersion medium (D) is equal to or higher than the boiling point of water, and the step of removing water (C) in the W / O emulsion includes an operation of heating the W / O emulsion. 10. A method for producing organic-inorganic composite particles according to 10.
JP2009155182A 2009-06-30 2009-06-30 Organic-inorganic composite particles, method for producing the same, and method for producing organic-inorganic composite hydrogel particles Expired - Fee Related JP5398383B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2009155182A JP5398383B2 (en) 2009-06-30 2009-06-30 Organic-inorganic composite particles, method for producing the same, and method for producing organic-inorganic composite hydrogel particles

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2009155182A JP5398383B2 (en) 2009-06-30 2009-06-30 Organic-inorganic composite particles, method for producing the same, and method for producing organic-inorganic composite hydrogel particles

Publications (2)

Publication Number Publication Date
JP2011012107A true JP2011012107A (en) 2011-01-20
JP5398383B2 JP5398383B2 (en) 2014-01-29

Family

ID=43591323

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2009155182A Expired - Fee Related JP5398383B2 (en) 2009-06-30 2009-06-30 Organic-inorganic composite particles, method for producing the same, and method for producing organic-inorganic composite hydrogel particles

Country Status (1)

Country Link
JP (1) JP5398383B2 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2013027668A1 (en) * 2011-08-19 2015-03-19 国立大学法人九州大学 Ion concentration gradient generation system, apparatus, method, and temperature-responsive electrolyte material
WO2015125968A1 (en) * 2014-02-24 2015-08-27 日産化学工業株式会社 Method for producing gel
WO2017164003A1 (en) * 2016-03-22 2017-09-28 Dic株式会社 Method for producing organic-inorganic composite hydrogel
WO2019009025A1 (en) * 2017-07-03 2019-01-10 Dic株式会社 Method for producing organic-inorganic hybrid hydrogel
WO2020129606A1 (en) * 2018-12-17 2020-06-25 Dic株式会社 Organic-inorganic composite hydrogel precursor composition, and organic-inorganic composite hydrogel
CN112851971A (en) * 2020-12-31 2021-05-28 合肥工业大学 Preparation method of hyperelastic nano composite hydrogel resistant to high and low temperatures and organic solvents
WO2022050331A1 (en) * 2020-09-04 2022-03-10 Dic株式会社 Organic-inorganic complex liquid dispersion and method for producing same

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002053629A (en) * 2000-05-29 2002-02-19 Kawamura Inst Of Chem Res Organic/inorganic complex hydrogel and method for producing the same
JP2002336694A (en) * 2001-05-15 2002-11-26 Kawamura Inst Of Chem Res Aqueous solution absorbing material and sanitary goods
JP2005075852A (en) * 2003-08-28 2005-03-24 Dainippon Ink & Chem Inc Method for producing highly absorbing resin
JP2007068696A (en) * 2005-09-06 2007-03-22 Kawamura Inst Of Chem Res Sterilization method and biocompatible material
JP2007297550A (en) * 2006-05-02 2007-11-15 Kawamura Inst Of Chem Res Moisture conditioning deodorant and method for producing the same
WO2008108277A1 (en) * 2007-03-01 2008-09-12 Nippon Shokubai Co., Ltd. Granulated water absorbent containing water-absorbing resin as the main component
JP2009046553A (en) * 2007-08-17 2009-03-05 Kawamura Inst Of Chem Res Method for producing organic inorganic composite hydrogel having carboxylic acid group or sulfonic acid group
JP2009114391A (en) * 2007-11-08 2009-05-28 San-Dia Polymer Ltd Absorbable resin particle, method for producing the same, absorbable body and absorbable article, containibg the resin particle

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002053629A (en) * 2000-05-29 2002-02-19 Kawamura Inst Of Chem Res Organic/inorganic complex hydrogel and method for producing the same
JP2002336694A (en) * 2001-05-15 2002-11-26 Kawamura Inst Of Chem Res Aqueous solution absorbing material and sanitary goods
JP2005075852A (en) * 2003-08-28 2005-03-24 Dainippon Ink & Chem Inc Method for producing highly absorbing resin
JP2007068696A (en) * 2005-09-06 2007-03-22 Kawamura Inst Of Chem Res Sterilization method and biocompatible material
JP2007297550A (en) * 2006-05-02 2007-11-15 Kawamura Inst Of Chem Res Moisture conditioning deodorant and method for producing the same
WO2008108277A1 (en) * 2007-03-01 2008-09-12 Nippon Shokubai Co., Ltd. Granulated water absorbent containing water-absorbing resin as the main component
JP2009046553A (en) * 2007-08-17 2009-03-05 Kawamura Inst Of Chem Res Method for producing organic inorganic composite hydrogel having carboxylic acid group or sulfonic acid group
JP2009114391A (en) * 2007-11-08 2009-05-28 San-Dia Polymer Ltd Absorbable resin particle, method for producing the same, absorbable body and absorbable article, containibg the resin particle

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2013027668A1 (en) * 2011-08-19 2015-03-19 国立大学法人九州大学 Ion concentration gradient generation system, apparatus, method, and temperature-responsive electrolyte material
JP2018046001A (en) * 2011-08-19 2018-03-22 国立大学法人九州大学 Ion concentration gradient generation system, device, and method, and temperature-responsive electrolyte material
US10137409B2 (en) 2011-08-19 2018-11-27 Kyushu University, National University Corporation System, device and method for generating ion concentration gradient, and temperature-responsive electrolyte material
US10695714B2 (en) 2011-08-19 2020-06-30 Kyushu University, National University Corporation System, device, and method for producing ion concentration gradient, and temperature-responsive electrolyte material
US10300432B2 (en) 2011-08-19 2019-05-28 Kyushu University, National University Corporation System, device, and method for producing ion concentration gradient, and temperature-responsive electrolyte material
WO2015125968A1 (en) * 2014-02-24 2015-08-27 日産化学工業株式会社 Method for producing gel
JPWO2015125968A1 (en) * 2014-02-24 2017-03-30 日産化学工業株式会社 Method for producing gel
US10059812B2 (en) 2014-02-24 2018-08-28 Nissan Chemical Industries, Ltd. Method for producing gel
WO2017164003A1 (en) * 2016-03-22 2017-09-28 Dic株式会社 Method for producing organic-inorganic composite hydrogel
JPWO2017164003A1 (en) * 2016-03-22 2018-04-05 Dic株式会社 Method for producing organic-inorganic composite hydrogel
JPWO2019009025A1 (en) * 2017-07-03 2019-07-04 Dic株式会社 Method of producing organic-inorganic composite hydrogel
WO2019009025A1 (en) * 2017-07-03 2019-01-10 Dic株式会社 Method for producing organic-inorganic hybrid hydrogel
WO2020129606A1 (en) * 2018-12-17 2020-06-25 Dic株式会社 Organic-inorganic composite hydrogel precursor composition, and organic-inorganic composite hydrogel
JPWO2020129606A1 (en) * 2018-12-17 2021-02-15 Dic株式会社 Organic-inorganic composite hydrogel precursor composition, and organic-inorganic composite hydrogel
CN113195569A (en) * 2018-12-17 2021-07-30 Dic株式会社 Organic-inorganic composite hydrogel precursor composition and organic-inorganic composite hydrogel
CN113195569B (en) * 2018-12-17 2023-10-03 Dic株式会社 Organic-inorganic composite hydrogel precursor composition and organic-inorganic composite hydrogel
WO2022050331A1 (en) * 2020-09-04 2022-03-10 Dic株式会社 Organic-inorganic complex liquid dispersion and method for producing same
CN116018357A (en) * 2020-09-04 2023-04-25 富士胶片株式会社 Organic-inorganic composite dispersion and method for producing same
CN112851971A (en) * 2020-12-31 2021-05-28 合肥工业大学 Preparation method of hyperelastic nano composite hydrogel resistant to high and low temperatures and organic solvents
CN112851971B (en) * 2020-12-31 2022-09-16 合肥工业大学 Preparation method of hyperelastic nano composite hydrogel resistant to high and low temperatures and organic solvents

Also Published As

Publication number Publication date
JP5398383B2 (en) 2014-01-29

Similar Documents

Publication Publication Date Title
JP5398383B2 (en) Organic-inorganic composite particles, method for producing the same, and method for producing organic-inorganic composite hydrogel particles
Dutta et al. Temperature, pH and redox responsive cellulose based hydrogels for protein delivery
Thakur et al. Recent trends in hydrogels based on psyllium polysaccharide: a review
Kiatkamjornwong Superabsorbent polymers and superabsorbent polymer composites
JP4759165B2 (en) Organic / inorganic composite hydrogel and method for producing the same
Bai et al. Monodisperse hydrophilic polymer microspheres having carboxylic acid groups prepared by distillation precipitation polymerization
Zhao et al. Mechanically strong and thermosensitive macromolecular microsphere composite poly (N-isopropylacrylamide) hydrogels
Xu et al. A novel multi-responsive polyampholyte composite hydrogel with excellent mechanical strength and rapid shrinking rate
Noreen et al. A review on grafting of hydroxyethylcellulose for versatile applications
Rabiee et al. Polyacrylamide-based polyampholytes and their applications
JP5246855B2 (en) Method for producing organic-inorganic composite hydrogel having carboxylate structure or carboxyanion structure group
JP2002053762A (en) Organic and inorganic composite hydrogel and its producing method
Hebeish et al. Radically new cellulose nanocomposite hydrogels: Temperature and pH responsive characters
Hu et al. Preparation and characterization of novel cationic pH-responsive poly (N, N′-dimethylamino ethyl methacrylate) microgels
Chang et al. Construction of mixed micelle with cross-linked core and dual responsive shells
Janovák et al. Swelling properties of copolymer hydrogels in the presence of montmorillonite and alkylammonium montmorillonite
Li et al. Synthesis and self-assembly behavior of thermoresponsive poly (oligo (ethylene glycol) methyl ether methacrylate)-POSS with tunable lower critical solution temperature
Cao et al. Fabrication of self-healing nanocomposite hydrogels with the cellulose nanocrystals-based Janus hybrid nanomaterials
Vdovchenko et al. Effect of heterogeneous and homogeneous polymerisation on the structure of pNIPAm nanogels
JPS6173704A (en) Production of highly water-absorptive resin
Sand et al. Effects of reaction parameters on water absorption of poly (itaconic acid) superabsorbent particles synthesized by inverse suspension polymerization
Li et al. Silica-based Janus nanosheets for self-healing nanocomposite hydrogels
Reguieg et al. Nanocomposite hydrogels based on water soluble polymer and montmorillonite-Na+
Sadeghi et al. Synthesis of novel polysaccharide-based superabsorbent hydro gels via graft copolymerization of vinylic monomers onto kappa-carrageenan
Bajpai et al. Inverse suspension polymerization of poly (methacrylic acid-co-partially neutralized acrylic acid) superabsorbent hydrogels: synthesis and water uptake behavior

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20120627

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20130212

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20130213

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20130410

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20130604

A711 Notification of change in applicant

Free format text: JAPANESE INTERMEDIATE CODE: A711

Effective date: 20130710

RD03 Notification of appointment of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7423

Effective date: 20130710

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20130724

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20130924

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20131022

R150 Certificate of patent or registration of utility model

Ref document number: 5398383

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

LAPS Cancellation because of no payment of annual fees